Location of Repository

Cellular interactions of airway smooth muscle and human lung mast cells

By Lucy Woodman

Abstract

Asthma is characterized by variable airflow obstruction, airway hyperresponsiveness (AHR), inflammation and remodeling. Mast cells (MC) co-localise to airway structures such as epithelium and airway smooth muscle (ASM) - the latter is a key determinant of AHR. Our group has reported that the CXCL10/CXCR3 axis is important in MC migration towards ASM, MCs adhere to ASM predominately via CADM-1 and this interaction promotes MC survival and proliferation. Whether there are other important mechanisms driving MC localization, ASM migration, and how MCs affect ASM differentiation is uncertain. \ud We sought to examine i) chemokine concentrations in airway secretions in eosinophilic bronchitis (EB), and asthma, and their effects on MC migration ii) CCR3 mediated ASM migration, iii) effects of MC–ASM co-culture on ASM differentiation. \ud Bronchoalveolar lavage (BAL) CXCL10 and CXCL8 concentrations were increased in subjects with EB compared to asthmatics and controls; were chemotactic for MCs and was attenuated by CXCR1 or CXCR3 inhibition. CCL11 mediated ASM migration and wound healing, but had no effect on proliferation or survival. Co-culture with β-tryptase or MCs degraded CCL11, and inhibited CCL11-mediated ASM migration. In vitro co-culture of ASM cells with β-tryptase or MCs increased ASM-derived TGF-β1 secretion, α-smooth muscle actin (α-SMA) expression and agonist-provoked contraction. Promotion to a more contractile phenotype was inhibited by leupeptin and TGF-β1 neutralization, suggesting ASM differentiation was driven by the autocrine release of TGF-β1 in response to β-tryptase. Importantly, in vivo, in asthmatic bronchial biopsies, intensity of α-SMA expression was strongly related to the number of MCs within or adjacent to ASM bundles. \ud In conclusion, CXCL8 and CXCL10 are important in MC migration to the epithelium, but CCL11 is unlikely to be important in ASM migration. MCs drive ASM differentiation to a more contractile phenotype via autocrine release of TGF-β1, which may contribute to the disordered airway physiology in asthma

Publisher: University of Leicester
Year: 2009
OAI identifier: oai:lra.le.ac.uk:2381/7382

Suggested articles

Preview

Citations

  1. (1980). (p-Amidinophenyl)methanesulfonyl fluoride, an irreversible inhibitor of serine proteases. Biochemistry
  2. (2005). [The role of mast cells in allergic inflammation--from the view point of innate immune system involvement]. Nippon Yakurigaku Zasshi
  3. (2004). 4 and IL-13 after segmental allergen challenge and their effects on alpha-smooth muscle actin and collagen III synthesis by primary human lung fibroblasts. Clin Exp Allergy
  4. (2006). A et al. Airway smooth muscle and mast cell-derived CC chemokine ligand 19 mediate airway smooth muscle migration in asthma. Am J Respir Crit Care Med
  5. (2000). A et al. Impaired vascular contractility and blood pressure homeostasis in the smooth muscle alpha-actin null mouse.
  6. (2008). A Holy Grail of asthma management: toward understanding how long-acting beta(2)-adrenoceptor agonists enhance the clinical efficacy of inhaled corticosteroids.
  7. (1994). A mannose receptor mediates mannosyl-rich glycoprotein-induced mitogenesis in bovine airway smooth muscle cells.
  8. (1999). A role for p38(MAPK)/HSP27 pathway in smooth muscle cell migration.
  9. (1996). A theoretical analysis of the effect of airway smooth muscle load on airway narrowing.
  10. (1981). Acid hydrolases and tryptase from secretory granules of dispersed human lung mast cells.
  11. (1984). Actin and tropomyosin variants in smooth muscles. Dependence on tissue type.
  12. (2005). Activation of human lung mast cells by monomeric immunoglobulin E. Eur Respir J
  13. (2004). Activation of mast cells by double-stranded RNA: evidence for activation through Toll-like receptor 3. J Allergy Clin Immunol
  14. (2007). Advances in asthma and allergy genetics in
  15. (2001). Airway epithelial cells release eosinophil survival-promoting factors (GM-CSF) after stimulation of proteinase-activated receptor 2. J Allergy Clin Immunol
  16. (1995). Airway hyperresponsiveness in asthma: a problem of limited smooth muscle relaxation with inspiration.
  17. (1998). Airway hyperresponsiveness in asthma: not just a matter of airway inflammation. Thorax
  18. (1993). Airway mucosal inflammation even in patients with newly diagnosed asthma. Am Rev Respir Dis
  19. (2004). Airway remodeling: a comparison between fatal and nonfatal asthma.
  20. (1994). Airway Smooth Muscle : Development and Regulation of Contractility.
  21. (2001). Airway smooth muscle cell proliferation is increased in asthma. Am J Respir Crit Care Med
  22. (2003). Airway smooth muscle: contraction and beyond.
  23. (2003). Airway structural alterations selectively associated with severe asthma.
  24. (2002). Akkaya A et al. T cells and eosinophils cooperate in the induction of bronchial epithelial cell apoptosis in asthma.
  25. (2001). Alpha-smooth muscle actin expression upregulates fibroblast contractile activity. Mol Biol Cell
  26. (1996). Alveolar tissue inflammation in asthma.
  27. (1998). and monocyte chemoattractant protein 1 production by cultured human airway smooth muscle cells. Cytokine
  28. (2006). Aneurysm syndromes caused by mutations in the TGF-beta receptor.
  29. (1990). Assembly of amino-terminally deleted desmin in vimentin-free cells.
  30. (2007). Asthma control during the year after bronchial thermoplasty.
  31. (2000). Autocrine thrombospondin partially mediates TGF-beta1-induced proliferation of vascular smooth muscle cells.
  32. (2004). Basic fibroblast growth factor antagonizes transforming growth factor-beta1-induced smooth muscle gene expression through extracellular signal-regulated kinase 1/2 signaling pathway activation. Arterioscler Thromb Vasc Biol
  33. (2005). beta1-Integrins mediate enhancement of airway smooth muscle proliferation by collagen and fibronectin.
  34. Bronchial Asthma. Principles and Practice of Medicine.
  35. (1994). Bronchial biopsy evidence for leukocyte infiltration and upregulation of leukocyte-endothelial cell adhesion molecules 6 hours after local allergen challenge of sensitized asthmatic airways.
  36. (2007). Bronchial inflammation and airway responses to deep inspiration in asthma and chronic obstructive pulmonary disease. Am J Respir Crit Care Med
  37. (2007). Bronchial smooth muscle remodeling involves calcium-dependent enhanced mitochondrial biogenesis in asthma.
  38. Bronchoalveolar lavage fluid concentrations of transforming growth factor (TGF)-beta1, TGF-beta2, interleukin
  39. (2004). Burden of allergic disease in the UK: secondary analyses of national databases. Clin Exp Allergy
  40. (1994). Caldesmon and calponin phosphorylation in regulation of smooth muscle contraction.
  41. (1986). Carbachol-induced protein phosphorylation changes in bovine tracheal smooth muscle.
  42. (2004). CCL11 (Eotaxin) induces CCR3-dependent smooth muscle cell migration. Arterioscler Thromb Vasc Biol
  43. (2002). CCR2 deficiency decreases intimal hyperplasia after arterial injury. Arterioscler Thromb Vasc Biol
  44. (2005). CCR3 expression and function in asthmatic airway smooth muscle cells.
  45. (2004). CCR4 ligands are up-regulated in the airways of atopic asthmatics after segmental allergen challenge. Eur Respir J
  46. (1988). Cell cycle versus density dependence of smooth muscle alpha actin expression in cultured rat aortic smooth muscle cells.
  47. (1998). Cellular and extracellular biology of the latent transforming growth factor-beta binding proteins. Matrix Biol
  48. (1997). Cellular communication and the action of growth factors during wound healing. J Wound Care
  49. (1993). Cellular hypertrophy and hyperplasia of airway smooth muscles underlying bronchial asthma. A 3-D morphometric study. Am Rev Respir Dis
  50. (2002). Changes in biophysical and biochemical properties of single bronchial smooth muscle cells from asthmatic subjects. Am J Physiol Lung Cell Mol Physiol
  51. (2004). chemokines in allergen-induced asthma.
  52. (1998). Chronic cough resembles asthma with IL-5 and granulocyte-macrophage colony-stimulating factor gene expression in bronchoalveolar cells.
  53. (1989). Chronic cough: eosinophilic bronchitis without asthma. Lancet
  54. (2008). Clinical asthma syndromes and important asthma mimics. Respir Care
  55. (2007). Clinical relevance of airway remodelling in airway diseases.
  56. (2008). Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med
  57. (2003). Collagen-induced resistance to glucocorticoid anti-mitogenic actions: a potential explanation of smooth muscle hyperplasia in the asthmatic remodelled airway.
  58. (2003). Comparison of airway immunopathology of eosinophilic bronchitis and asthma. Thorax
  59. (2003). Concerted expression of eotaxin-1, eotaxin-2, and eotaxin-3 in human bronchial epithelial cells. Cell Immunol
  60. (2006). Connective tissue growth factor and vascular endothelial growth factor from airway smooth muscle interact with the extracellular matrix. Am J Physiol Lung Cell Mol Physiol
  61. (2006). Connective tissue growth factor induces extracellular matrix in asthmatic airway smooth muscle. Am J Respir Crit Care Med
  62. (1999). Constitutive and cytokine-stimulated expression of eotaxin by human airway smooth muscle cells. Am J Respir Crit Care Med
  63. (2001). Contractile protein expression in bladder smooth muscle is a marker of phenotypic modulation after outlet obstruction in the rabbit model.
  64. (2004). Contribution of eotaxin-1 to eosinophil chemotactic activity of moderate and severe asthmatic sputum. Am J Respir Crit Care Med
  65. (2004). Cough is an airway itch?
  66. (2007). Cultured lung fibroblasts from ovalbumin-challenged "asthmatic" mice differ functionally from normal.
  67. (2004). CXCL16 signals via Gi, phosphatidylinositol 3-kinase, Akt, I kappa B kinase, and nuclear factor-kappa B and induces cell-cell adhesion and aortic smooth muscle cell proliferation.
  68. (2003). Cyclic AMP-mobilizing agents and glucocorticoids modulate human smooth muscle cell migration.
  69. (2003). CysLT1 receptor upregulation by TGF-beta and IL-13 is associated with bronchial smooth muscle cell proliferation in response to LTD4. J Allergy Clin Immunol
  70. (2004). Cysteinyl leukotrienes and their receptors: cellular distribution and function in immune and inflammatory responses.
  71. (1992). Cytokines in symptomatic asthma airways.
  72. (2004). Decreased expression of smooth muscle alpha-actin results in decreased contractile function of the mouse bladder.
  73. (2007). Deep inspiration-induced changes in lung volume decrease with severity of asthma. Respir Med
  74. (2005). Definition, diagnosis, disease types, and classification of asthma. Int Arch Allergy Immunol
  75. (2000). Demonstration of mast cell chemotactic activity in bronchoalveolar lavage fluid collected from asthmatic patients before and during pollen season. J Allergy Clin Immunol
  76. (1999). Demonstration that human mast cells arise from a bipotential progenitor cell that is CD34+, c-kit+, and expresses aminopeptidase N (CD13).
  77. (2004). Desmin: a major intermediate filament protein essential for the structural integrity and function of muscle. Exp Cell Res
  78. (2008). Development of a novel chemokine-mediated in vivo T cell recruitment assay.
  79. (2003). Developmentally regulated expression of calponin isoforms and the effect of h2-calponin on cell proliferation.
  80. (2005). Differences in airway remodeling between subjects with severe and moderate asthma. J Allergy Clin Immunol
  81. (1984). Differences in the behavior of cytoplasmic granules and lipid bodies during human lung mast cell degranulation.
  82. (2005). Differential expression of CCR3 and CXCR3 by human lung and bone marrow-derived mast cells: implications for tissue mast cell migration.
  83. (2005). Differential proteomic analysis of bronchoalveolar lavage fluid in asthmatics following segmental antigen challenge. Mol Cell Proteomics
  84. (2006). Differential regulation of neurotrophin expression in human bronchial smooth muscle cells. Respir Res
  85. (1987). Direct evidence of a role for mast cells in the pathogenesis of antigen-induced bronchoconstriction.
  86. (1998). Dissociation between airway inflammation and airway hyperresponsiveness in allergic asthma.
  87. (1990). Distinct transforming growth factor-beta (TGF-beta) receptor subsets as determinants of cellular responsiveness to three TGF-beta isoforms.
  88. (2002). Distribution and degranulation of airway mast cells in normal and asthmatic subjects. Eur Respir J
  89. (1987). Distribution and modulation of the cellular receptor for transforming growth factor-beta.
  90. (1999). Divergent differentiation paths in airway smooth muscle culture: induction of functionally contractile myocytes.
  91. (1987). Diversity in smooth muscle thin filament composition. Biochim Biophys Acta
  92. (2001). Effects of growth factors and extracellular matrix on survival of human airway smooth muscle cells.
  93. (1998). Effects of LTD4 on human airway smooth muscle cell proliferation, matrix expression, and contraction In vitro: differential sensitivity to cysteinyl leukotriene receptor antagonists.
  94. (2002). Effects of rhinovirus infection on histamine and cytokine production by cell lines from human mast cells and basophils.
  95. (2004). Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma. Am J Respir Crit Care Med
  96. (2000). Eosinophilic bronchitis - what is it and why is it important? Clin Exp Allergy
  97. (1999). Eosinophilic bronchitis is an important cause of chronic cough.
  98. (2000). Eosinophils in asthma and other allergic diseases. Br Med Bull
  99. (2001). Eotaxin expression after segmental allergen challenge in subjects with atopic asthma. Am J Respir Crit Care Med
  100. (2007). Epithelial cell proliferation contributes to airway remodeling in severe asthma. Am J Respir Crit Care Med
  101. (2001). Expression and function of proteinase-activated receptor 2 in human bronchial smooth muscle. Am J Respir Crit Care Med
  102. (1998). Expression and release of interleukin-8 by human airway smooth muscle cells: inhibition by Th-2 cytokines and corticosteroids.
  103. (2003). Expression of connective tissue growth factor in asthmatic airway smooth muscle cells. Am J Respir Crit Care Med
  104. (2001). Expression of the C-C chemokine receptor CCR3 in human airway epithelial cells.
  105. (2002). Expression of the interleukin-8 receptors CXCR1 and CXCR2 on cord-blood-derived cultured human mast cells.
  106. (1992). Expression of the potent inflammatory cytokines, granulocyte-macrophage-colony-stimulating factor and interleukin-6 and interleukin-8, in bronchial epithelial cells of patients with asthma.
  107. (2006). Extracellular matrix regulates enhanced eotaxin expression in asthmatic airway smooth muscle cells. Am J Respir Crit Care Med
  108. (2000). Extrapancreatic trypsin-2 cleaves proteinase-activated receptor-2. Biochem Biophys Res Commun
  109. (2000). Family size, infection and atopy: the first decade of the "hygiene hypothesis". Thorax
  110. (2005). FcepsilonRI-mediated amphiregulin production by human mast cells increases mucin gene expression in epithelial cells.
  111. (2006). Fibroblast growth factor 2 and transforming growth factor beta1 synergism in human bronchial smooth muscle cell proliferation.
  112. (2003). Fractalkine (CX3CL1) stimulated by nuclear factor kappaB (NF-kappaB)-dependent inflammatory signals induces aortic smooth muscle cell proliferation through an autocrine pathway.
  113. (2004). Fractalkine/CX3CL1 production by human airway smooth muscle cells: induction by IFN-gamma and TNF-alpha and regulation by TGF-beta and corticosteroids. Am J Physiol Lung Cell Mol Physiol
  114. (2006). Fraktalkine produced by airway smooth muscle cells contributes to mast cell recruitment in asthma.
  115. (2001). Functional effects of protease-activated receptor-2 stimulation on human airway smooth muscle.
  116. (2008). Genes in asthma: new genes and new ways. Curr Opin Allergy Clin Immunol
  117. Global Initiative For Asthma (GINA). Global Strategy For Asthma Management And Prevention.
  118. Global Initiative For Asthma (GINA). Pocket Guide For Asthma Management And Prevention. www.ginaasthma.com .
  119. (2008). Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J
  120. (2001). Glycosylation and the activation of proteinase-activated receptor 2 (PAR(2)) by human mast cell tryptase.
  121. (2002). Glycosylation of human proteinaseactivated receptor-2 (hPAR2): role in cell surface expression and signalling.
  122. (2001). h-Caldesmon expression effectively distinguishes endometrial stromal tumors from uterine smooth muscle tumors.
  123. (2005). h2-Calponin is regulated by mechanical tension and modifies the function of actin cytoskeleton.
  124. (1997). High expression of the chemokine receptor CCR3 in human blood basophils. Role in activation by eotaxin, MCP-4, and other chemokines.
  125. (2007). Histamine and tryptase modulate asthmatic airway smooth muscle GM-CSF and RANTES release. Eur Respir J
  126. (1990). Histamine stimulates proliferation of airway smooth muscle and induces c-fos expression.
  127. (1997). Human airway smooth muscle cells express and release RANTES in response to T helper 1 cytokines: regulation by T helper 2 cytokines and corticosteroids.
  128. (2004). Human beta-tryptase: detection and characterization of the active monomer and prevention of tetramer reconstitution by protease inhibitors. Biochemistry
  129. (1998). Human betatryptase is a ring-like tetramer with active sites facing a central pore. Nature
  130. (1999). Human bronchial smooth muscle cells in culture produce stem cell factor. Eur Respir J
  131. (1995). Human heart mast cells. Isolation, purification, ultrastructure, and immunologic characterization.
  132. (1991). Human mast cell carboxypeptidase. Selective localization to MCTC cells.
  133. (1995). Human mast cell chymase and leukocyte elastase release latent transforming growth factor-beta 1 from the extracellular matrix of cultured human epithelial and endothelial cells.
  134. (2000). Human mast cell tryptase stimulates the release of an IL-8-dependent neutrophil chemotactic activity from human umbilical vein endothelial cells (HUVEC). Clin Exp Immunol
  135. (2005). Human neutrophil elastase induces hypersecretion of mucin from well-differentiated human bronchial epithelial cells in vitro via a protein kinase C{delta}-mediated mechanism.
  136. (2004). Hyperplasia of smooth muscle in mild to moderate asthma without changes in cell size or gene expression. Am J Respir Crit Care Med
  137. (1990). Identification of a cathepsin G-like proteinase in the MCTC type of human mast cell.
  138. (2003). Identification of circulating fibrocytes as precursors of bronchial myofibroblasts in asthma.
  139. (2008). Identification of pendrin as a common mediator for mucus production in bronchial asthma and chronic obstructive pulmonary disease.
  140. (2002). IL-13 and IL-4 cause eotaxin release in human airway smooth muscle cells: a role for ERK. Am J Physiol Lung Cell Mol Physiol
  141. (2008). IL-13 induces a bronchial epithelial phenotype that is profibrotic. Respir Res
  142. (2005). IL-4-expressing bronchoalveolar T cells from asthmatic and healthy subjects preferentially express CCR 3 and CCR 4. J Allergy Clin Immunol
  143. (2004). IL-8 inhibits isoproterenol-stimulated ciliary beat frequency in bovine bronchial epithelial cells.
  144. (2003). Immunological and clinical changes in allergic asthmatics following treatment with omalizumab. Int Arch Allergy Immunol
  145. (1997). Increased expression of eotaxin in bronchoalveolar lavage and airways of asthmatics contributes to the chemotaxis of eosinophils to the site of inflammation.
  146. (2002). Increased mast cells and neutrophils in submucosal mucous glands and mucus plugging in patients with asthma. Thorax
  147. (2000). Increased numbers of both airway basophils and mast cells in sputum after allergen inhalation challenge of atopic asthmatics. Am J Respir Crit Care Med
  148. (2003). Increasing prevalence of asthma in UK primary care during the 1990s. Int J Tuberc Lung Dis
  149. (1996). Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements.
  150. (1999). Induced sputum eicosanoid concentrations in asthma.
  151. (2004). Induced sputum inflammatory mediator concentrations in chronic cough.
  152. (2000). Induced sputum inflammatory mediator concentrations in eosinophilic bronchitis and asthma.
  153. (2007). Inflammation of bronchial smooth muscle in allergic asthma. Thorax
  154. (2007). Inflammatory cell microlocalisation and airway dysfunction: cause and effect? Eur Respir J
  155. (1990). Inflammatory markers in bronchoalveolar lavage and in bronchial biopsy in asthma during remission. Chest
  156. (2003). Inhibition of induction of myofibroblasts by interferon gamma in a human fibroblast cell line. Int Immunopharmacol
  157. (2001). Inhibition of mast cell tryptase by inhaled APC 366 attenuates allergen-induced late-phase airway obstruction in asthma.
  158. (2005). Inhibitors of mast cell tryptase beta as therapeutics for the treatment of asthma and inflammatory disorders. Pulm Pharmacol Ther
  159. (1997). Inhibitory effects of an anti-IgE antibody E25 on allergen-induced early asthmatic response. Am J Respir Crit Care Med
  160. (2004). Integrin alphaVbeta6-mediated activation of latent TGF-beta requires the latent TGF-beta binding protein-1.
  161. (1994). Interleukin-1 beta inhibits airway smooth muscle contraction via epithelium-dependent mechanism.
  162. (1989). Interleukin-1 mitogenic activity for fibroblasts and smooth muscle cells is due to PDGF-AA. Science
  163. (2003). Interleukin-4 and -13 expression is co-localized to mast cells within the airway smooth muscle in asthma. Clin Exp Allergy
  164. (1998). Interleukin-4 inhibits mitogen-induced proliferation of human airway smooth muscle cells in culture.
  165. (1994). Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways: evidence for the human mast cell as a source of these cytokines.
  166. (1993). Intraepithelial mast cells in allergic and nonallergic asthma. Assessment using bronchial brushings. Am Rev Respir Dis
  167. (2003). Ion channel gene expression in human lung, skin, and cord blood-derived mast cells.
  168. (2001). Is asthma really due to a polarized T cell response toward a helper T cell type 2 phenotype? Am J Respir Crit Care Med
  169. (1994). Latent transforming growth factor-beta 1 associates to fibroblast extracellular matrix via latent TGF-beta binding protein.
  170. (1997). Latent transforming growth factor-beta: structural features and mechanisms of activation. Kidney Int
  171. (2001). Leukotriene D(4)-induced Rho-mediated actin reorganization in human bronchial smooth muscle cells.
  172. (2008). Leukotriene D4-induced, epithelial cell-derived transforming growth factor beta1 in human bronchial smooth muscle cell proliferation. Clin Exp Allergy
  173. (2005). LTD4 induces hyperresponsiveness to histamine in bovine airway smooth muscle: role of SRATPase Ca2+ pump and tyrosine kinase. Am J Physiol Lung Cell Mol Physiol
  174. (1998). Lung smooth muscle differentiation.
  175. (2004). Lysophosphatidic acid accelerates the development of human mast cells. Blood
  176. (1989). Macrophage production of transforming growth factor beta and fibroblast collagen synthesis in chronic pulmonary inflammation.
  177. (2008). Making the diagnosis of asthma. Respir Care
  178. (1993). Mammalian calponin. Identification and expression of genetic variants.
  179. (1992). Marked goblet cell hyperplasia with mucus accumulation in the airways of patients who died of severe acute asthma attack. Chest
  180. (1996). Markers of airway smooth muscle cell phenotype.
  181. (2006). Mast cell beta-tryptase selectively cleaves eotaxin and RANTES and abrogates their eosinophil chemotactic activities.
  182. (2006). Mast cell migration to Th2 stimulated airway smooth muscle from asthmatics. Thorax
  183. (1996). Mast cell tryptase is a mitogen for epithelial cells. Stimulation of IL-8 production and intercellular adhesion molecule-1 expression.
  184. (1997). Mast cell tryptase potentiates histamine-induced contraction in human sensitized bronchus. Eur Respir J
  185. (2004). Mast cell tryptase: a review of its physiology and clinical significance. Anaesthesia
  186. (2008). Mast cells are activated by Leishmania mexicana LPG and regulate the disease outcome depending on the genetic background of the host. Parasite Immunol
  187. (2006). Mast cells are essential intermediaries in regulatory T-cell tolerance. Nature
  188. (2000). Mast cells enhance contraction of threedimensional collagen lattices by fibroblasts by cell-cell interaction: role of stem cell factor/c-kit. Immunology
  189. (2005). Mast cells in the development of adaptive immune responses. Nat Immunol
  190. (2000). Mast cells migrate, but do not degranulate, in response to fractalkine, a membrane-bound chemokine expressed constitutively in diverse cells of the skin.
  191. (2004). Mast cells promote fibroblast populated collagen lattice contraction through gap junction intercellular communication. Wound Repair Regen
  192. (2004). Mast cells: the Jekyll and Hyde of tumor growth. Trends Immunol
  193. (2002). Mast-cell infiltration of airway smooth muscle in asthma.
  194. (1999). MCP-4), and C-C chemokine receptor 3 expression in bronchial biopsies from atopic and nonatopic (Intrinsic) asthmatics.
  195. (2007). Mechanisms of induction of airway smooth muscle hyperplasia by transforming growth factor-beta. Am J Physiol Lung Cell Mol Physiol
  196. (1997). Mechanisms underlying TNF-alpha effects on agonist-mediated calcium homeostasis in human airway smooth muscle cells.
  197. (1983). Mediators of hypersensitivity and inflammatory cells in the pathogenesis of bronchial asthma.
  198. (2001). Mild and moderate asthma is associated with airway goblet cell hyperplasia and abnormalities in mucin gene expression. Am J Respir Crit Care Med
  199. (1991). Modulation of actin isoform expression in cultured arterial smooth muscle cells by heparin and culture conditions. Arterioscler Thromb
  200. (2003). Modulation of enzymatic activity of human mast cell tryptase and chymase by protease inhibitors. Acta Pharmacol Sin
  201. (2000). Molecular Cell Biology.
  202. (1999). Molecular consequences of human mast cell activation following immunoglobulin E-high-affinity immunoglobulin E receptor (IgE-FcepsilonRI) interaction. Biochem Pharmacol
  203. (2008). Molecular mechanics of smooth muscle contractile proteins in airway hyperresponsiveness and asthma. Proc Am Thorac Soc
  204. (1997). Monocyte chemotactic protein-1 is a proinflammatory chemokine in rat skin injection sites and chemoattracts basophilic granular cells. Int Immunol
  205. (1981). Moses Maimonides' treatise on asthma. Thorax
  206. (2005). Multi-dimensional phenotyping: towards a new taxonomy for airway disease. Clin Exp Allergy
  207. (2006). Multiple roles of alpha-smooth muscle actin in mechanotransduction. Exp Cell Res
  208. (1993). Myosin isoform expression in developing and remodeling rat lung.
  209. (1996). Myosin light chain kinase: an actin-binding protein that regulates an ATP-dependent interaction with myosin. Trends Pharmacol Sci
  210. (2001). Neointimal and tubulointerstitial infiltration by recipient mesenchymal cells in chronic renal-allograft rejection.
  211. (2000). Nerve growth factor functions as a chemoattractant for mast cells through both mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling pathways. Blood
  212. (2003). Neutrophil serine proteinases activate human nonepithelial cells to produce inflammatory cytokines through protease-activated receptor 2. J Immunol
  213. (2002). New insights into the relationship between airway inflammation and asthma. Clin Sci (Lond)
  214. (2003). New insights into the role of the mast cell in asthma. Clin Exp Allergy
  215. (2007). Noneosinophilic asthma: a distinct clinical and pathologic phenotype.
  216. (2006). Number of pericryptal fibroblasts correlates with density of distinct mast cell phenotypes in the crypt lamina propria of human duodenum: implications for the homeostasis of villous architecture. Anat Rec A Discov Mol Cell Evol Biol
  217. (1997). Of mites and men: trypsin-like proteases in the lungs.
  218. (2000). Overexpression of eotaxin and the CCR3 receptor in human atherosclerosis: using genomic technology to identify a potential novel pathway of vascular inflammation. Circulation
  219. (2006). p38 inhibitors prevent TGF-beta-induced myofibroblast transdifferentiation in human tenon fibroblasts. Invest Ophthalmol Vis Sci
  220. (2008). Pathogenesis of asthma. Clin Exp Allergy
  221. (1996). Pathology of mild, severe, and fatal asthma.
  222. (1996). PDGF isoform-induced proliferation and receptor expression in human cultured airway smooth muscle cells.
  223. (2001). Peripheral blood fibrocytes: differentiation pathway and migration to wound sites.
  224. (1995). Plasminogen deficiency causes severe thrombosis but is compatible with development and reproduction. Genes Dev
  225. (1995). Platelet-derived growth factor in asthma. Allergy
  226. (2000). Production of basic fibroblast growth factor and interleukin 6 by human smooth muscle cells following infection with Chlamydia pneumoniae. Infect Immun
  227. (2001). Protease-activated receptors in human airways: upregulation of PAR-2 in respiratory epithelium from patients with asthma.
  228. (2003). Proteinase-activated receptor-2 and human lung epithelial cells: disarming by neutrophil serine proteinases.
  229. (1998). Proteinase-activated receptors: novel mechanisms of signaling by serine proteases.
  230. (1981). Purification and characterization of smooth muscle myosin light chain kinase.
  231. (1987). Quantitation of histamine, tryptase, and chymase in dispersed human T and TC mast cells.
  232. (2006). Recent developments in CCR3 antagonists. Curr Opin Drug Discov Devel
  233. (2001). Reduced Smad3 protein expression and altered transforming growth factor-beta1-mediated signaling in cystic fibrosis epithelial cells.
  234. (2006). Regional fibroblast heterogeneity in the lung: implications for remodeling. Am J Respir Crit Care Med
  235. (1995). Regulation of differentiation of vascular smooth muscle cells. Physiol Rev
  236. (1999). Regulation of lysyl oxidase, collagen, and connective tissue growth factor by TGF-beta1 and detection in human gingiva. Lab Invest
  237. (2002). Regulation of smooth muscle actin expression and contraction in adult human mesenchymal stem cells. Exp Cell Res
  238. (2004). Regulation of TNF-alpha- and IFN-gamma-induced CXCL10 expression: participation of the airway smooth muscle in the pulmonary inflammatory response in chronic obstructive pulmonary disease.
  239. (1994). Regulation of type II alveolar epithelial cell proliferation by TGF-beta during bleomycin-induced lung injury in rats.
  240. (2001). Release of biologically active TGF-beta from airway smooth muscle cells induces autocrine synthesis of collagen.
  241. (2003). Release of both CCR4-active and CXCR3-active chemokines during human allergic pulmonary late-phase reactions. J Allergy Clin Immunol
  242. (2001). Remodeling in asthma and chronic obstructive lung disease.
  243. (2005). Role of contractile prostaglandins and Rho-kinase in growth factor-induced airway smooth muscle contraction. Respir Res
  244. (2001). Role of human airway smooth muscle in altered extracellular matrix production in asthma. Clin Exp Pharmacol Physiol
  245. (2008). Scottish Intercollegiate Guidelines Network, British Thoracic Society.
  246. (2002). Selective CCL5/RANTES-induced mast cell migration through interactions with chemokine receptors
  247. (2002). Selective induction of eotaxin release by interleukin-13 or interleukin-4 in human airway smooth muscle cells is synergistic with interleukin-1beta and is mediated by the interleukin-4 receptor alpha-chain. Am J Respir Crit Care Med
  248. (2004). Smad3 null mice develop airspace enlargement and are resistant to TGF-beta-mediated pulmonary fibrosis.
  249. (2003). small-molecule inhibitors of human mast cell tryptase. Antiasthmatic action of a dipeptide-based transition-state analogue containing a benzothiazole ketone.
  250. (1998). Smooth muscle actin and myosin expression in cultured airway smooth muscle cells.
  251. (1991). Smooth muscle alphaactin is a marker for hair follicle dermis in vivo and in vitro.
  252. (2003). Smooth muscle contraction and relaxation. Adv Physiol Educ
  253. (2005). Smooth muscle length adaptation and actin filament length: a network model of the cytoskeletal dysregulation.
  254. (2005). Smooth muscle-specific alpha tropomyosin is a marker of fully differentiated smooth muscle in lung.
  255. (2005). Some structural determinants of the antiproliferative effect of heparin-like molecules on human airway smooth muscle.
  256. (1999). Stem cell factor-dependent survival, proliferation and enhanced releasability of purified mature mast cells isolated from human intestinal tissue. Int Arch Allergy Immunol
  257. (2001). Stem cell factor-induced migration of mast cells requires p38 mitogen-activated protein kinase activity. Experimental Cell Research
  258. (2007). Suppression of alpha smooth muscle actin expression by IFN-gamma in established myofibroblast cell lines.
  259. (2005). Surface CD88 functionally distinguishes the MCTC from the MCT type of human lung mast cell. J Allergy Clin Immunol
  260. (1995). survival of cultured human mast cells. Blood
  261. (2004). Susceptibility of mast cell-deficient W/Wv mice to pristane-induced experimental lupus nephritis. Immunol Lett
  262. (2008). Sutcliffe A et al. Human airway smooth muscle promotes human lung mast cell survival, proliferation, and constitutive activation: cooperative roles for CADM1, stem cell factor, and IL-6.
  263. (2006). Synergistic roles of platelet-derived growth factor-BB and interleukin-1beta in phenotypic modulation of human aortic smooth muscle cells.
  264. (2004). Synthetic responses in airway smooth muscle.
  265. (1992). Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature
  266. (2007). Targeted mast cell silencing protects against joint destruction and angiogenesis in experimental arthritis in mice. Arthritis Rheum
  267. (1995). Targeting TGF-beta for treatment of disease. Nat Med
  268. (2006). TGF-beta1 increases proliferation of airway smooth muscle cells by phosphorylation of map kinases. Respir Res
  269. (2000). TGF-beta1 stimulates IL-8 release, COX-2 expression, and PGE(2) release in human airway smooth muscle cells.
  270. (2002). TH2 cytokine expression in bronchoalveolar lavage fluid T lymphocytes and bronchial submucosa is a feature of asthma and eosinophilic bronchitis.
  271. (2003). TH2 Cytokine-enhanced and TGF-beta-enhanced vascular endothelial growth factor production by cultured human airway smooth muscle cells is attenuated by IFN-gamma and corticosteroids.
  272. (2000). The contractile apparatus and mechanical properties of airway smooth muscle. Eur Respir J
  273. (1996). The costs of asthma.
  274. (2005). The CXCL10/CXCR3 axis mediates human lung mast cell migration to asthmatic airway smooth muscle.
  275. (2001). The differentiation and function of myofibroblasts is regulated by mast cell mediators.
  276. (1999). The direct effects of heparin and protamine on canine tracheal smooth muscle tone. Anesth Analg
  277. (2000). The effect of age and duration of disease on airway structure in fatal asthma.
  278. (1997). The effect of an anti-IgE monoclonal antibody on the early- and late-phase responses to allergen inhalation in asthmatic subjects. Am J Respir Crit Care Med
  279. (2008). The effect of TGF-beta2 on elastin, type VI collagen, and components of the proteolytic degradation system in human optic nerve astrocytes. Invest Ophthalmol Vis Sci
  280. (1985). The function of myosin and myosin light chain kinase phosphorylation in smooth muscle. Annu Rev Pharmacol Toxicol
  281. (2006). The genetics of asthma: ADAM33 as an example of a susceptibility gene. Proc Am Thorac Soc
  282. (1999). The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell
  283. (2003). The integrin alphavbeta3 is a receptor for the latency-associated peptides of transforming growth factors beta1 and beta3. Biochem J
  284. (2001). The lack of the bronchoprotective and not the bronchodilatory ability of deep inspiration is associated with airway hyperresponsiveness. Am J Respir Crit Care Med
  285. (1996). The mast cell as a source of cytokines in asthma.
  286. (2007). The reclassification of asthma based on subphenotypes. Curr Opin Allergy Clin Immunol
  287. (1999). The T cellspecific CXC chemokines IP-10, Mig, and I-TAC are expressed by activated human bronchial epithelial cells.
  288. (1999). The unique 5-flanking region of the human basic calponin gene. Hypertens Res
  289. (1997). The use of induced sputum to investigate airway inflammation. Thorax
  290. (2001). Thoracic Society guidelines on diagnostic flexible bronchoscopy. Thorax
  291. (1993). Thrombospondin 1 is a tight-binding competitive inhibitor of neutrophil cathepsin G. Determination of the kinetic mechanism of inhibition and localization of cathepsin G binding to the thrombospondin 1 type 3 repeats.
  292. (1998). Thrombospondin-1 is a major activator of TGF-beta1 in vivo. Cell
  293. (2000). Tissue factor- and factor X-dependent activation of protease-activated receptor 2 by factor VIIa.
  294. (1994). Transforming growth factor beta: a matter of life and death.
  295. (1997). Transforming growth factor-beta 1 in asthma. Measurement in bronchoalveolar lavage fluid. Am J Respir Crit Care Med
  296. (2006). Transforming growth factor-beta induces airway smooth muscle hypertrophy.
  297. (2006). Transforming growth factor-beta signaling through the Smad proteins: role in systemic sclerosis. Autoimmun Rev
  298. (2001). Transforming growth factor-betamediated mast cell migration depends on mitogen-activated protein kinase activity. Cellular Signalling
  299. (1989). Transgenic expression of the muscle-specific intermediate filament protein desmin in nonmuscle cells.
  300. (2001). Triggering the induction of myofibroblast and fibrogenesis by airway epithelial shedding.
  301. (2008). Tryptase activates TGFbeta in human airway smooth muscle cells via direct proteolysis. Biochem Biophys Res Commun
  302. (2002). Tryptase activates the mitogenactivated protein kinase/activator protein-1 pathway in human peripheral blood eosinophils, causing cytokine production and release.
  303. (2001). Tryptase and agonists of PAR-2 induce the proliferation of human airway smooth muscle cells.
  304. (2002). Tryptase: potential role in airway inflammation and remodeling.
  305. (2002). Tryptase's potent mitogenic effects in human airway smooth muscle cells are via nonproteolytic actions.
  306. (1999). Tryptasechymase double-positive human mast cells express the eotaxin receptor CCR3 and are attracted by CCR3-binding chemokines.
  307. (2003). Tryptasestimulated human airway smooth muscle cells induce cytokine synthesis and mast cell chemotaxis.
  308. (2001). Tsicopoulos A et al. Expression of IFN-gamma-inducible protein; monocyte chemotactic proteins 1, 3, and 4; and eotaxin in TH1- and TH2-mediated lung diseases. J Allergy Clin Immunol
  309. (2003). Tumor necrosis factor alpha modulates airway smooth muscle function via the autocrine action of interferon beta.
  310. (2000). Tumor necrosis factor-alpha enhances mRNA expression and secretion of interleukin-6 in cultured human airway smooth muscle cells.
  311. (1986). Two types of human mast cells that have distinct neutral protease compositions.
  312. (2003). Urokinase potentiates PDGF-induced chemotaxis of human airway smooth muscle cells.
  313. (2004). Viral-induced T helper type 1 responses enhance allergic disease by effects on lung dendritic cells. Nat Immunol
  314. (2001). Voltage-dependent and calcium-activated ion channels in the human mast cell line HMC-1.
  315. (2005). What the asthma end points we know and love do and do not tell us.

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.