Location of Repository

The Role of Properdin in Cellular and Humoral Responses – in vitro and in vivo analyses

By Nur’Ain Salehen

Abstract

Due to third party copyright restrictions the published articles have been removed from the appendix of the electronic version of this thesis. The unabridged version can be consulted, on request, at the University of Leicester’s David Wilson Library.Complement is part of the innate immune defence. It can be activated via three pathways, the classical pathway, the lectin pathway, and the alternative pathway. It comprises soluble factors and receptors. Properdin (Factor P) is a soluble component of the alternative complement pathway which acts as an important positive regulator of complement activation that stabilises the alternative pathway convertases (C3bBb) and C3bBb5b in the feedback loop of the alternative pathway, protecting them from rapid inactivation. The thesis is interested to see the role of properdin in cellular and humoral immune responses by in vitro and in vivo analyses.\ud Firstly, properdin was examined for its global activity by characterisation of promoter activity of the human gene for properdin which involved using bioinformatics and molecular biology. The promoter activity was measured by dual-luciferase reporter system. The findings appeared to have activity in the 670bp properdin plasmid construct in U937 non-LPS transfection but the transfection upon LPS stimulation was not successful. Next, by using a properdin-deficient mouse line as a tool, it is interested to investigate the role of properdin in immunity by using properdin-deficient mice as model in pneumococcal vaccination studies, in vitro characterisation of dendritic cells and mycobacterium infectious studies in bone marrow-derived dendritic cells culture.\ud In vaccination studies demonstrated that vaccination proved efficacious as both properdin-deficient and WT had increased in total IgM level and specific IgM level after the vaccination as measured by commercial ELISA for total IgM and specific ELISA for PPS2 IgM. In the absence of properdin, specific anti-polysaccharide antibodies of the IgM type are made. Vaccinated properdin-deficient mice do not differ from wild type in their immunoglobulin response to the pneumococcal polysaccharide vaccine. Meanwhile properdin-deficiency had a benefit in survival, independent of vaccination.\ud For the in vitro characterisation of dendritic cells, dendritic cells are derived from bone marrow and spleen culture, and flow cytometry measured dendritic cells phenotype surface markers. Both bone marrow and spleen dendritic cells derived from properdin deficient mice are impaired to be activated and mature as dendritic cells compared to wild type mice. The study presently concludes that the presence of properdin is essential to allow dendritic cells to develop their activated phenotype and properdin is a relevant player in dendritic cell mediated immune response.\ud Further investigation of function of generated BM-derived DC of WT and properdin-deficient towards Mycobacterium tuberculosis and Mycobacterium bovis BCG.\ud In overall findings of mycobacterial viability, secretion of TNF-α and intracellular containment of mycobacterium in BMDC, it is concluded that properdin has no role of in the immune response of BM-derived DC towards Mycobacterium tuberculosis and Mycobacterium bovis BCG.\ud In conclusion, having properdin is essential to help the complement system as part of defence mechanism against infection. Additionally, properdin could play a ‘double-edged’ role

Publisher: University of Leicester
Year: 2011
OAI identifier: oai:lra.le.ac.uk:2381/10068

Suggested articles

Preview

Citations

  1. (1965). [On the use of yeasts in chronic bronchial inflammations].
  2. (1996). A life stage of particleladen rat dendritic cells in vivo: their terminal division, active phagocytosis, and translocation from the liver to the draining lymph.
  3. (2007). A reduced antigen load in vivo, rather than weak inflammation, causes a substantial delay in CD8+ T cell priming against Mycobacterium bovis (bacillus Calmette-Guerin).
  4. (2006). A role for dendritic cells in the dissemination of mycobacterial infection.
  5. (1988). A second variant of properdin deficiency: the detection of properdin at low concentrations in affected males.
  6. (1999). A soluble gradient of the neuropeptide secretoneurin promotes the transendothelial migration of monocytes in vitro.
  7. (1983). Activation of complement via the alternative pathway.
  8. (1997). Activation of human dendritic cells following infection with Mycobacterium tuberculosis.
  9. (2008). Activator-specific requirement of properdin in the initiation and amplification of the alternative pathway complement.
  10. (1999). An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow.
  11. (1992). An association between homozygous C3 deficiency and low levels of anti-pneumococcal capsular polysaccharide antibodies.
  12. (2001). An overview of the immune system.
  13. (2004). Analysis of the germinal center reaction and in vivo long-lived plasma cells.
  14. (1989). Analysis of the natural polymeric forms of human properdin and their functions in complement activation.
  15. (1996). Apoptosis of mouse dendritic cells is triggered by listeriolysin, the major virulence determinant of Listeria monocytogenes.
  16. (2002). B-1a B cells that link the innate and adaptive immune responses are lacking in the absence of the spleen.
  17. (2000). B-cell activation by T-cell-independent type 2 antigens as an integral part of the humoral immune response to pathogenic microorganisms.
  18. (2005). B-cell kinetics in humans: rapid turnover of peripheral blood memory cells.
  19. (2005). B-lymphocytes, innate immunity, and autoimmunity.
  20. (2001). Bacterial polysaccharides as vaccines--immunity and chemical characterization.
  21. (1999). Band T-cell immune responses to pneumococcal conjugate vaccines: divergence between carrier- and polysaccharide-specific immunogenicity.
  22. (1988). Biosynthesis of complement factor P (properdin) by the human premonocyte cell line (U-937).
  23. (1989). Biosynthesis of properdin.
  24. (1983). C3b deposition during activation of the alternative complement pathway and the effect of deposition on the activating surface.
  25. (2001). Cell-type specific regulation of thrombospondin-1 expression and its promoter activity by regulatory agents.
  26. (2002). Chapter 7: Conclusion Chapter 7: Conclusion Properdin (Factor P) as a component of the alternative complement pathway which acts as
  27. (1995). Characterization of mutant forms of recombinant human properdin lacking single thrombospondin type I repeats. Identification of modules important for function.
  28. (1997). Characterization of the 5' flanking region of the human complement factor H gene.
  29. (1992). Characterization of the human properdin gene.
  30. (1995). Cloning and characterization of the cDNA encoding guinea-pig properdin: a comparison of properdin from three species.
  31. (2007). Complement activation pathways: a bridge between innate and adaptive immune responses in asthma.
  32. (2003). Complement and infectious diseases.
  33. (2007). Complement C5a anaphylatoxin is an innate determinant of dendritic cell-induced Th1 immunity to Mycobacterium bovis BCG infection in mice.
  34. (2007). Complement components, regulators and receptors are produced by human monocyte-derived dendritic cells.
  35. (1991). Complement deficiency and disease.
  36. (2005). Complement dependency of splenic localization of pneumococcal polysaccharide and conjugate vaccines.
  37. (1993). Complement factor I and cofactors in control of complement system convertase enzymes.
  38. (2003). Complement resistance mechanisms of streptococci.
  39. (2001). Complement. First of two parts.
  40. (1987). Congenital properdin deficiency and meningococcal infection.
  41. (2003). Constrained intracellular survival of Mycobacterium tuberculosis in human dendritic cells.
  42. (2008). Control of dendritic cell maturation and function by triiodothyronine.
  43. (2006). CRM197-conjugated serogroup C meningococcal capsular polysaccharide, but not the native polysaccharide, induces persistent antigen-specific memory B cells.
  44. (1984). Cross-reactions of polysaccharides of staphylococci and streptococci in antipneumococcal and other antisera.
  45. (2000). Cutting edge: complementactivating complex of ficolin and mannose-binding lectin-associated serine protease.
  46. (2001). Cutting edge: germinal centers can be induced in the absence of T cells.
  47. (2009). Deficiency of mannose-binding lectin greatly increases antibody response in a mouse model of vaccination.
  48. (1997). Dendritic cell development and maturation.
  49. (1997). Dendritic cell maturation is required for initiation of the immune response.
  50. (1993). Dendritic cell progenitors phagocytose particulates, including bacillus Calmette-Guerin organisms, and sensitize mice to mycobacterial antigens in vivo.
  51. (2000). Dendritic cell regulation of TH1-TH2 development.
  52. (2006). Dendritic cell synthesis of C3 is required for full T cell activation and development of a Th1 phenotype.
  53. (2001). Dendritic cells (I): Biological functions.
  54. (1998). Dendritic cells and the control of immunity.
  55. (2002). Dendritic cells are host cells for mycobacteria in vivo that trigger innate and acquired immunity.
  56. (2007). Dendritic cells: understanding immunogenicity.
  57. (2006). Differentiation and 3D migration of the human myeloid leukaemia cell line U937 and primary monocytic cells by endogenous protein factors.
  58. (2003). Disparity in functional activity between serum anticapsular antibodies induced in adults by immunization with an investigational group A and C Neisseria meningitidis-diphtheria toxoid conjugate vaccine and by a polysaccharide vaccine.
  59. (1999). Does properdin crosslink the cellular and the humoral immune response?
  60. (1994). Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colonystimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha.
  61. (2003). Enzyme-linked immunosorbent assay for quantitation of human antibodies to pneumococcal polysaccharides.
  62. (2001). Expression and characterisation of the thrombospondin type I repeats of human properdin.
  63. (2004). Expression of glutathione S-transferase P1-1 in leukemic cells is regulated by inducible AP-1 binding.
  64. (1987). Familial properdin deficiency and fatal meningococcemia. Correction of the bactericidal defect by vaccination.
  65. (2001). Fate of Mycobacterium tuberculosis within murine dendritic cells.
  66. (1981). Formation of the initial C3 convertase of the alternative complement pathway. Acquisition of C3b-like activities by spontaneous hydrolysis of the putative thioester in native C3.
  67. (2004). Functional differences in IgG anti-polysaccharide antibodies elicited by immunization of mice with C3d versus ovalbumin conjugates of pneumococcal serotype 14 capsular polysaccharide.
  68. (1992). Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor.
  69. (1991). Genetic and physical mapping around the properdin P gene.
  70. (1991). Granulocyte functions and Neisseria meningitidis: influence of properdin-deficient serum.
  71. (1985). Guidelines on the recognition of pain, distress and discomfort in experimental animals and an hypothesis for assessment. Vet Rec,
  72. (1998). Heterogeneity of mouse spleen dendritic cells: in vivo phagocytic activity, expression of macrophage markers, and subpopulation turnover.
  73. (2007). Hospitalizations and deaths caused by methicillin-resistant Staphylococcus aureus, United States,
  74. (1994). Human liver-derived HEP G2 cells produce functional properdin.
  75. (1992). Human mannose-binding protein is identical to a component of Ra-reactive factor.
  76. (1989). Human marginal zone B cells are not an activated B cell subset: strong expression of CD21 as a putative mediator for rapid B cell activation.
  77. (2006). Human monocyte-derived dendritic cells are a source of several complement proteins.
  78. (1997). Human properdin deficiency has a heterogeneous genetic background.
  79. (2009). Identification of a simple chemical structure associated with protective human antibodies against multiple pneumococcal serogroups.
  80. (2004). IL-10-conditioned dendritic cells, decommissioned for recruitment of adaptive immunity, elicit innate inflammatory gene products in response to danger signals.
  81. (2007). Immune modulation of human dendritic cells by complement.
  82. (1989). Immune response to tetravalent meningococcal vaccine: opsonic and bactericidal functions of normal and properdin deficient sera.
  83. (2003). Immunity to Streptococcus pneumoniae: Factors affecting production and efficacy.
  84. (2000). Immunobiology of dendritic cells.
  85. (1992). Immunogenicity of conjugate vaccines consisting of pneumococcal capsular polysaccharide types 6B, 14, 19F, and 23F and a meningococcal outer membrane protein complex.
  86. (2008). Impaired dendritic cell differentiation and maturation in the absence of C3.
  87. (2005). In vivo depletion of CD11c+ cells delays the CD4+ T cell response to Mycobacterium tuberculosis and exacerbates the outcome of infection.
  88. (2005). In vivo humoral immune responses to isolated pneumococcal polysaccharides are dependent on the presence of associated TLR ligands.
  89. (1992). Induction of IgG3 secretion by interferon gamma: a model for T cell-independent class switching in response to T cell-independent type 2 antigens.
  90. (2005). Innate immune defense against pneumococcal pneumonia requires pulmonary complement component C3.
  91. (1994). Intraperitoneal immunization of human subjects with tetanus toxoid induces specific antibodysecreting cells in the peritoneal cavity and in the circulation, but fails to elicit a secretory IgA response.
  92. (2006). Lack of induced co-stimulation as a result of complement receptor 2 (CR2) ligation on mouse splenic B cells.
  93. (2003). Latent tuberculosis: mechanisms of host and bacillus that contribute to persistent infection.
  94. (1989). Localization of the properdin structural locus to Xp11.23-Xp21.1.
  95. (1993). Macrophage phagocytosis of virulent but not attenuated strains of Mycobacterium tuberculosis is mediated by mannose receptors in addition to complement receptors.
  96. (1998). Mast cells mediate acute inflammatory responses to implanted biomaterials.
  97. (2004). Maturation of dendritic cells abrogates C1q production in vivo and in vitro.
  98. (2005). Maturation requirements for dendritic cells in T cell stimulation leading to tolerance versus immunity.
  99. (1997). Maturation stages of mouse dendritic cells in growth factor-dependent longterm cultures.
  100. (1984). Molecular architecture of human properdin, a positive regulator of the alternative pathway of complement.
  101. (2002). Mouse and human dendritic cell subtypes.
  102. (1996). Mouse decay-accelerating factor: selective and tissue-specific induction by estrogen of the gene encoding the glycosylphosphatidylinositol-anchored form.
  103. (2009). Multiple routes of complement activation by Mycobacterium bovis BCG.
  104. (2008). Mycobacteria and innate cells: critical encounter for immunogenicity.
  105. (1998). Mycobacterium tuberculosis and the complement system.
  106. (2002). Mycobacterium tuberculosis induces differential cytokine production from dendritic cells and macrophages with divergent effects on naive T cell polarization.
  107. (2000). Mycobacterium tuberculosis infection in complement receptor 3-deficient mice.
  108. (2007). Mycobacterium tuberculosis infects dendritic cells with high frequency and impairs their function in vivo.
  109. (2000). Natural antibodies and complement link innate and acquired immunity.
  110. (1991). Normal human serum depleted of C1q, factor D and properdin: its use in studies of complement activation.
  111. (1997). Origin, maturation and antigen presenting function of dendritic cells.
  112. (2007). p150/95 (CD11c/CD18) expression is required for the development of experimental autoimmune encephalomyelitis.
  113. (1990). Phagocytosis of Mycobacterium tuberculosis is mediated by human monocyte complement receptors and complement component C3.
  114. (2007). Pneumococcal capsular polysaccharide vaccine-mediated protection against serotype 3 Streptococcus pneumoniae in immunodeficient mice.
  115. (1991). Pneumococcal polysaccharides complexed with C3d bind to human B lymphocytes via complement receptor type 2.
  116. (2005). Porins limit the intracellular persistence of Mycobacterium smegmatis.
  117. (1980). Presidential address to American Association of Immunologists in
  118. (1989). Primary in situ immune response in popliteal lymph nodes and spleen of mice after subcutaneous immunization with thymus-dependent or thymus-independent (type 1 and 2) antigens.
  119. (2000). Production of protective human antipneumococcal antibodies by transgenic mice with human immunoglobulin loci.
  120. (1994). Promoter elements of the mouse complement C4 gene critical for transcription activation and start site location.
  121. (2007). Properdin can initiate complement activation by binding specific target surfaces and providing a platform for de novo convertase assembly.
  122. (1999). Properdin deficiency and meningococcal disease--identifying those most at risk.
  123. (1982). Properdin deficiency in a family with fulminant meningococcal infections.
  124. (1999). Properdin deficiency in a large Swiss family: identification of a stop codon in the properdin gene, and association of meningococcal disease with lack of the IgG2 allotype marker G2m(n). Clin Exp Immunol,
  125. (2008). Properdin deficiency in murine models of nonseptic shock.
  126. (1999). Properdin deficiency: molecular basis and disease association.
  127. (2008). Properdin in immunity: In vitro and in vivo investigations.
  128. (2008). Properdin plays a protective role in polymicrobial septic peritonitis.
  129. (1993). Properdin, a positive regulator of complement activation, is expressed in human T cell lines and peripheral blood T cells.
  130. (2000). Properdin, the positive regulator of complement, is highly C-mannosylated.
  131. (1988). Properdin, the terminal complement components, thrombospondin and the circumsporozoite protein of malaria parasites contain similar sequence motifs.
  132. (1975). Properdin: binding to C3b and stabilization of the C3b-dependent C3 convertase.
  133. (1975). Properdin: initiation of alternative complement pathway.
  134. (1999). Protection against aerosol Mycobacterium tuberculosis infection using Mycobacterium bovis Bacillus Calmette Guerin-infected dendritic cells.
  135. (1998). Protection against meningococcal serogroup ACYW disease in complement-deficient individuals vaccinated with the tetravalent meningococcal capsular polysaccharide vaccine.
  136. (1996). Regulation of alternative pathway activation and C3a production by adipose cells.
  137. (2005). Regulation of B lymphocyte activation by complement C3 and the B cell coreceptor complex.
  138. (1996). Regulation of dendritic cell numbers and maturation by lipopolysaccharide in vivo.
  139. (1980). Relation of putative thioester bond in C3 to activation of the alternative pathway and the binding of C3b to biological targets of complement.
  140. (2000). Responsive site on the thrombospondin-1 promotor to down-regulation by phorbol 12-myristate 13-acetate in porcine aortic endothelial cells.
  141. Role and mechanism of action of complement in regulating T cell immunity.
  142. (1992). Role of cell wall polysaccharide in the assessment of IgG antibodies to the capsular polysaccharides of Streptococcus pneumoniae in childhood.
  143. (2001). Role of complement in Mycobacterium avium pathogenesis: in vivo and in vitro analyses of the host response to infection in the absence of complement component C3.
  144. (2007). Role of dendritic cell synthesis of complement in the allospecific T cell response.
  145. (1991). Signals arising from antigen-presenting cells.
  146. (1999). Streptococcus pneumoniae.
  147. (1991). Structural features of the human C3 gene: intron/exon organization, transcriptional start site, and promoter region sequence.
  148. (1974). Studies on the sub-unit structure of human properdin.
  149. (2005). Susceptibility and resistance to pneumococcal disease in mice.
  150. (1978). Synthesis of factors D, B and P of the alternative pathway of complement activation, as well as of C3, by guinea-pig peritoneal macrophages in vitro.
  151. (2006). T-independent type II immune responses generate memory B cells.
  152. (2008). The alternative complement pathway revisited.
  153. (2003). The B cell receptor itself can activate complement to provide the complement receptor 1/2 ligand required to enhance B cell immune responses in vivo.
  154. (2004). The classical and alternative pathways of complement activation play distinct roles in spontaneous C3 fragment deposition and membrane attack complex (MAC) formation on human B lymphocytes.
  155. (2002). The classical pathway is the dominant complement pathway required for innate immunity to Streptococcus pneumoniae infection in mice.
  156. (2004). The complement system in regulation of adaptive immunity.
  157. (2004). The dimeric and trimeric solution structures of the multidomain complement protein properdin by X-ray scattering, analytical ultracentrifugation and constrained modelling.
  158. (1990). The distinct leukocyte integrins of mouse spleen dendritic cells as identified with new hamster monoclonal antibodies.
  159. (2003). The endothelium as physiological source of properdin: role of wall shear stress.
  160. (1998). The envelope layers of mycobacteria with reference to their pathogenicity.
  161. (2000). The immune system. First of two parts.
  162. (1982). The presence of sialic acid on two related bacterial polysaccharides determines the site of the primary immune response and the effect of complement depletion on the response in mice.
  163. (1975). The properdin pathway: mechanisms of complement activation and analogies to the classical pathway.
  164. (1954). The properdin system and immunity. I. Demonstration and isolation of a new serum protein, properdin, and its role in immune phenomena.
  165. (2008). The role of complement in the success of vaccination with conjugated vs. unconjugated polysaccharide antigen.
  166. The role of properdin in murine zymosan-induced arthritis.
  167. (2006). The role of properdin in the assembly of the alternative pathway C3 convertases of complement.
  168. (2002). Thrombospondin-1 differentially regulates release of IL-6 and IL-10 by human monocytic cell line U937.
  169. (2003). Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells.
  170. (2003). Toll-like receptors: balancing host resistance with immune tolerance.
  171. (1994). Transcriptional activation: a complex puzzle with few easy pieces.
  172. (1995). Transcriptional regulation of complement genes.
  173. (1994). Transcriptional regulation of the gene for the second component of human complement: promoter analysis.
  174. (1991). Virulence, immunity, and vaccine related to Streptococcus pneumoniae.
  175. (2004). Weakening of the repressive YY-1 site on the thrombospondin-1 promoter via cJun/YY-1 interaction.

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