Prominent Role Of Platelets In The Formation Of Circulating Neutrophil-red Cell Heterocellular Aggregates In Sickle Cell Anemia

[No abstract available]9911e214e217Hidalgo, A., Chang, J., Jang, J.E., Peired, A.J., Chiang, E.Y., Frenette, P.S., Heterotypic interactions enabled by polarized neutrophil microdomains mediate thromboinflammatory injury (2009) Nat Med, 15 (4), pp. 384-391Turhan, A., Jenab, P., Bruhns, P., Ravetch, J.V., Coller, B.S., Frenette, P.S., Intravenous immune globulin prevents venular vaso-occlusion in sickle cell mice by inhibiting leukocyte adhesion and the interactions between sickle erythrocytes and adherent leukocytes (2004) Blood, 103 (6), pp. 2397-2400Turhan, A., Weiss, L.A., Mohandas, N., Coller, B.S., Frenette, P.S., Primary role for adherent leukocytes in sickle cell vascular occlusion: A new paradigm (2002) Proc Natl Acad Sci USA, 99 (5), pp. 3047-3051May, A.E., Langer, H., Seizer, P., Bigalke, B., Lindemann, S., Gawaz, M., Platelet-leukocyte interactions in inflammation and atherothrombosis (2007) Semin Thromb Hemost, 33 (2), pp. 123-127Gawaz, M., Fateh-Moghadam, S., Pilz, G., Gurland, H.J., Werdan, K., Platelet activation and interaction with leucocytes in patients with sepsis or multiple organ failure (1995) Eur J Clin Invest, 25 (11), pp. 843-851Polanowska-Grabowska, R., Wallace, K., Field, J.J., Chen, L., Marshall, M.A., Figler, R., P-selectin-mediated platelet-neutrophil aggregate formation activates neutrophils in mouse and human sickle cell disease (2010) Art Thromb Vascular Biol, 30 (12), pp. 2392-2399Brittain, J.E., Knoll, C.M., Ataga, K.I., Orringer, E.P., Parise, L.V., Fibronectin bridges monocytes and reticulocytes via integrin alpha4beta1 (2008) Br J Haematol, 141 (6), pp. 872-881Chaar, V., Picot, J., Renaud, O., Bartolucci, P., Nzouakou, R., Bachir, D., Aggregation of mononuclear and red blood cells through an {alpha}4{beta}1-Lu/basal cell adhesion molecule interaction in sickle cell disease (2010) Haematologica, 95 (11), pp. 1841-1848Finnegan, E.M., Turhan, A., Golan, D.E., Barabino, G.A., Adherent leukocytes capture sickle erythrocytes in an in vitro flow model of vasoocclusion (2007) Am J Hematol, 82 (4), pp. 266-275Wun, T., Paglieroni, T., Tablin, F., Welborn, J., Nelson, K., Cheung, A., Platelet activation and platelet-erythrocyte aggregates in patients with sickle cell anemia (1997) J Lab Clin Med, 129 (5), pp. 507-516Hynes, R.O., Integrins: Versatility, modulation, and signaling in cell adhesion (1992) Cell, 69 (1), pp. 11-25Novelli, E.M., Kato, G.J., Ragni, M.V., Zhang, Y., Hildesheim, M.E., Nouraie, M., Plasma thrombospondin-1 is increased during acute sickle cell vaso-occlusive events and associated with acute chest syndrome, hydroxyurea therapy, and lower hemolytic rates (2012) Am J Hematol, 87 (3), pp. 326-330Proenca-Ferreira, R., Brugnerotto, A.F., Garrido, V.T., Dominical, V.M., Vital, D.M., Ribeiro Mde, F., Endothelial activation by platelets from sickle cell anemia patients (2014) PloS one, 9 (2)Kutlar, A., Ataga, K.I., McMahon, L., Howard, J., Galacteros, F., Hagar, W., A potent oral P-selectin blocking agent improves microcirculatory blood flow and a marker of endothelial cell injury in patients with sickle cell disease (2012) Am J Hematol, 87 (5), pp. 536-539Telen, M.J., Wun, T., McCavit, T.L., De Castro, L.M., Krishnamurti, L., Lanzkron, S., GMI 1070: Reduction In Time To Resolution Of Vaso-Occlusive Crisis and Decreased Opioid Use In a Prospective, Randomized, Multi-Center Double Blind, Adaptive Phase 2 Study In Sickle Cell Disease (2013) Blood, 122 (21), p. 7. , Abstrac

In vitro microfluidic model for the study of vaso-occlusive processes

Vaso-occlusion, responsible for much of the morbidity of sickle-cell disease, is a complex multicellular process, apparently triggered by leukocyte adhesion to the vessel wall. The microcirculation represents a major site of leukocyte-endothelial interactions and vaso-occlusive processes. We have developed a biochip with subdividing interconnecting microchannels that decrease in size (40 μm to 10 μm in width), for use in conjunction with a precise microfluidic device, to mimic cell flow and adhesion through channels of sizes that approach those of the microcirculation. The biochips were utilized to observe the dynamics of the passage of neutrophils and red blood cells, isolated from healthy and sickle-cell anemia (SCA) individuals, through laminin or endothelial adhesion molecule-coated microchannels at physiologically relevant rates of flow and shear stress. Obstruction of E-selectin/intercellular adhesion molecule 1-coated biochip microchannels by SCA neutrophils was significantly greater than that observed for healthy neutrophils, particularly in the microchannels of 40-15 μm in width. Whereas SCA red blood cells alone did not significantly adhere to, or obstruct, microchannels, mixed suspensions of SCA neutrophils and red blood cells significantly adhered to and obstructed laminin-coated channels. Results from this in vitro microfluidic model support a primary role for leukocytes in the initiation of SCA occlusive processes in the microcirculation. This assay represents an easy-to-use and reproducible in vitro technique for understanding molecular mechanisms and cellular interactions occurring in subdividing microchannels of widths approaching those observed in the microvasculature. The assay could hold potential for testing drugs developed to inhibit occlusive mechanisms such as those observed in SCA and thrombotic diseases.Vaso-occlusion, responsible for much of the morbidity of sickle-cell disease, is a complex multicellular process, apparently triggered by leukocyte adhesion to the vessel wall. The microcirculation represents a major site of leukocyte-endothelial interact43223228FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2010/17320-0; 2010/18386-4565036/01

Neutrophils Of Rheumatoid Arthritis Patients On Anti-tnf-α Therapy And In Disease Remission Present Reduced Adhesive Functions In Association With Decreased Circulating Neutrophil-attractant Chemokine Levels

Neutrophils participate in the initiation and progression of rheumatoid arthritis (RA) although the exact mechanisms responsible for neutrophil accumulation in rheumatoid joints are not understood. This study compared the adhesive and chemotactic functions of neutrophils from RA patients in activity (DAS28>3.2) and not in activity (DAS28<2.6) and observed the effects of different treatment approaches on these functions. Neutrophils were isolated from healthy controls (CON), and patients with active or inactive RA in use of therapy not specific for RA (NSAIDs), in use of DMARDs and in use of anti-TNF-α therapy. Adhesive and chemotactic properties were evaluated using in vitro assays; adhesion molecule expression was assessed by flow cytometry and real-time PCR and circulating chemokines were determined by ELISA. No significant alterations in the adhesive and chemotactic properties of neutrophils from active RA were observed when compared to CON neutrophils, independently of treatment regimen. In contrast, neutrophils from RA patients in disease remission presented reduced adhesive properties and a lower spontaneous chemotactic capacity, in association with decreased adhesion molecule expression, although profiles of alterations differed for those patients on DMARDs and those on anti-TNF-α therapy. Circulating levels of the major neutrophilic chemokines, IL-8 and epithelial neutrophil activating peptide-78, were also significantly decreased in those patients demonstrating a clinical response. Remission of RA appears to be associated with ameliorations in aspects important for neutrophil adhesion and chemotaxis; whether these alterations contribute to decrease neutrophil migration to the synovial fluid, with consequent improvements in the clinical manifestations of RA, remains to be determined. © 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.734309318Gaffo, A., Saag, K.G., Curtis, J.R., Treatment of rheumatoid arthritis (2006) Am J Health Syst Pharm, 63, pp. 2451-65Stanczyk, J., Kowalski, M.L., Grzegorczyk, J., RANTES and chemotactic activity in synovial fluids from patients with rheumatoid arthritis and osteoarthritis (2005) Mediators Inflamm, 2005, pp. 343-8Wright, H.L., Moots, R.J., Bucknall, R.C., Edwards, S.W., Neutrophil function in inflammation and inflammatory diseases (2010) Rheumatology (Oxford), 49, pp. 1618-31Cascao, R., Rosario, H.S., Souto-Carneiro, M.M., Fonseca, J.E., Neutrophils in rheumatoid arthritis: more than simple final effectors (2010) Autoimmun Rev, 9, pp. 531-5Cross, A., Bakstad, D., Allen, J.C., Neutrophil gene expression in rheumatoid arthritis (2005) Pathophysiology, 12, pp. 191-202Tarrant, T.K., Patel, D.D., Chemokines and leukocyte trafficking in rheumatoid arthritis (2006) Pathophysiology, 13, pp. 1-14Grespan, R., Fukada, S.Y., Lemos, H.P., CXCR2-specific chemokines mediate leukotriene B4-dependent recruitment of neutrophils to inflamed joints in mice with antigen-induced arthritis (2008) Arthritis Rheum, 58, pp. 2030-40Lemos, H.P., Grespan, R., Vieira, S.M., Prostaglandin mediates IL-23/IL-17-induced neutrophil migration in inflammation by inhibiting IL-12 and IFNgamma production (2009) Proc Natl Acad Sci USA, 106, pp. 5954-9Eyles, J.L., Hickey, M.J., Norman, M.U., A key role for G-CSF-induced neutrophil production and trafficking during inflammatory arthritis (2008) Blood, 112, pp. 5193-201Cross, A., Bucknall, R.C., Cassatella, M.A., Edwards, S.W., Moots, R.J., Synovial fluid neutrophils transcribe and express class II major histocompatibility complex molecules in rheumatoid arthritis (2003) Arthritis Rheum, 48, pp. 2796-806Cassatella, M.A., The production of cytokines by polymorphonuclear neutrophils (1995) Immunol Today, 16, pp. 21-6Burgos, R.A., Hidalgo, M.A., Figueroa, C.D., Conejeros, I., Hancke, J.L., New potential targets to modulate neutrophil function in inflammation (2009) Mini Rev Med Chem, 9, pp. 153-68Mpofu, S., Fatima, F., Moots, R.J., Anti-TNF-alpha therapies: they are all the same (aren't they?) (2005) Rheumatology, 44, pp. 271-3Capsoni, F., Sarzi-Puttini, P., Atzeni, F., Effect of adalimumab on neutrophil function in patients with rheumatoid arthritis (2005) Arthritis Res Ther, 7, pp. R250-5Arnett, F.C., Edworthy, S.M., Bloch, D.A., The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis (1988) Arthritis Rheum, 31, pp. 315-24English, D., Andersen BR Single-step separation of red blood cells. Granulocytes and mononuclear leukocytes on discontinuous density gradients of Ficoll-Hypaque (1974) J Immunol Methods, 5, pp. 249-52Assis, A., Conran, N., Canalli, A.A., Effect of cytokines and chemokines on sickle neutrophil adhesion to fibronectin (2005) Acta Haematol, 113, pp. 130-6Bradley, P.P., Priebat, D.A., Christensen, R.D., Rothstein, G., Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker (1982) J Invest Dermatol, 78, pp. 206-9Gambero, S., Canalli, A.A., Traina, F., Therapy with hydroxyurea is associated with reduced adhesion molecule gene and protein expression in sickle red cells with a concomitant reduction in adhesive properties (2007) Eur J Haematol, 78, pp. 144-51Vandesompele, J., De Preter, K., Pattyn, F., Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes (2002) Genome Biol, 3, pp. 341-3411Ley, K., Laudanna, C., Cybulsky, M.I., Nourshargh, S., Getting to the site of inflammation: the leukocyte adhesion cascade updated (2007) Nat Rev Immunol, 7, pp. 678-89Howe, G.B., Fordham, J.N., Brown, K.A., Currey, H.L., Polymorphonuclear cell function in rheumatoid arthritis and in Felty's syndrome (1981) Ann Rheum Dis, 40, pp. 370-5Sheehan, N.J., Brown, K.A., Perry, J.D., Adherence of rheumatoid polymorphonuclear cells (PMNs) to cultured endothelial cell monolayers (1987) Ann Rheum Dis, 46, pp. 93-7Hashimoto, H., Yamamura, M., Nishiya, K., Ota, Z., Impaired interleukin-8-dependent chemotaxis by synovial fluid polymorphonuclear leukocytes in rheumatoid arthritis (1994) Acta Med Okayama, 48, pp. 181-7Vollmer, K.L., Alberts, J.S., Carper, H.T., Mandell, G.L., Tumor necrosis factor-alpha decreases neutrophil chemotaxis to N-formyl-1-methionyl-1-leucyl-1-phenylalanine: analysis of single cell movement (1992) J Leukoc Biol, 52, pp. 630-6Verri Jr, W.A., Souto, F.O., Vieira, S.M., IL-33 induces neutrophil migration in rheumatoid arthritis and is a target of anti-TNF therapy (2010) Ann Rheum Dis, 69, pp. 1697-703Bond, A., Hay, F.C., L-selectin expression on the surface of peripheral blood leucocytes from rheumatoid arthritis patients is linked to disease activity (1997) Scand J Immunol, 46, pp. 312-6Smalley, D.M., Ley, K., L-selectin: mechanisms and physiological significance of ectodomain cleavage (2005) J Cell Mol Med, 9, pp. 255-66Lee, D., Caputo, K.E., Hammer, D.A., King, M.R., Adhesive dynamics simulations of the mechanical shedding of L-selectin from the neutrophil surface (2009) J Theor Biol, 260, pp. 27-30Eniola-Adefeso, O., Huang, R.B., Smith, C.W., Kinetics of LFA-1 mediated adhesion of human neutrophils to ICAM-1--role of E-selectin signaling post-activation (2009) Ann Biomed Eng, 37, pp. 737-48Hogg, N., Leitinger, B., Shape and shift changes related to the function of leukocyte integrins LFA-1 and Mac-1 (2001) J Leukoc Biol, 69, pp. 893-8Klimiuk, P.A., Sierakowski, S., Domyslawska, I., Chwiecko, J., Regulation of serum chemokines following infliximab therapy in patients with rheumatoid arthritis (2006) Clin Exp Rheumatol, 24, pp. 529-33Lun, S.W., Wong, C.K., Tam, L.S., Li, E.K., Lam, C.W., Decreased ex vivo production of TNF-alpha and IL-8 by peripheral blood cells of patients with rheumatoid arthritis after infliximab therapy (2007) Int Immunopharmacol, 7, pp. 1668-77Walz, A., Schmutz, P., Mueller, C., Schnyder-Candrian, S., Regulation and function of the CXC chemokine ENA-78 in monocytes and its role in disease (1997) J Leukoc Biol, 62, pp. 604-11Koch, A.E., Kunkel, S.L., Harlow, L.A., Epithelial neutrophil activating peptide-78: a novel chemotactic cytokine for neutrophils in arthritis (1994) J Clin Invest, 94, pp. 1012-8Wessels, J.A., Huizinga, T.W., Guchelaar, H.J., Recent insights in the pharmacological actions of methotrexate in the treatment of rheumatoid arthritis (2008) Rheumatology, 47, pp. 249-55Taylor, P.C., Pharmacology of TNF blockade in rheumatoid arthritis and other chronic inflammatory diseases (2010) Curr Opin Pharmacol, 10, pp. 308-1

Interactions of sickle red blood cells with neutrophils are stabilized on endothelial cell layers

sem informação5613840FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2010/18386-4; 10/17320-