Abstract
Microparticles (MPs) are believed to play an important role in inflammatory diseases such as rheumatoid arthritis (RA). Leukocytapheresis (LCAP) is one of the options available for the treatment of RA. We analyzed the levels of MPs in RA, by flow cytometry, especially in relation to the effect of LCAP. Twenty female patients with RA were recruited into this study. Six of the 20 patients with RA further received LCAP. Plasma levels of platelet-derived MPs were high in patients with RA and are correlated with disease activity. LCAP significantly improved RA in all six patients. The numbers of platelet-derived MPs significantly decreased after the first session of LCAP, which was probably due to direct removal by LCAP. Mean numbers of platelet-derived MPs after four sessions of LCAP markedly decreased. The numbers of granulocyte-derived MPs, which are suggested to have an anti-inflammatory effect, were markedly increased after the first session of LCAP. These data suggest that removal of platelet-derived MPs and increase of granulocyte-derived MPs are novel mechanisms of LCAP as effective treatment in RA.
Similar content being viewed by others
References
Firestein GS. Evolving concepts of rheumatoid arthritis. Nature. 2003;423:356–61.
Pap T, Muller-Ladner U, Gay RE, Gay S. Fibroblast biology role of synovial fibroblasts in the pathogenesis of rheumatoid arthritis. Arthritis Res. 2000;2:361–7.
Tarner IH, Müller-Ladner U, Gay S. Emerging targets of biologic therapies for rheumatoid arthritis. Nat Clin Pract Rheumatol. 2007;3:336–45.
Distler JH, Pisetsky DS, Huber LC, Kalden JR, Gay S, Distler O. Microparticles as regulators of inflammation. Novel players of cellular crosstalk in the rheumatic disease. Arthritis Rheum. 2005;52:3337–48.
Gasser O, Schifferli JA. Microparticles released by human neutrophils adhere to erythrocytes in the presence of complement. Exp Cell Res. 2005;307:381–7.
Ratajczak J, Wysoczynski M, Hayek F, Janowska-Wieczorek A, Ratajczak MZ. Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. Leukemia. 2006;20:1487–95.
Martinez MC, Tesse A, Zobairi F, Andriantsitohaina R. Shed membrane microparticles from circulating from vascular cells in resulting vascular function. Am J Physiol Heart Circ Physiol. 2005;288:1004–9.
Berckmans RJ, Nieuwland R, Tak PP, Boing AN, Romijn FP, Kraan MC, et al. Cell-derived microparticles in synovial fluid from inflamed arthritic joints support coagulation exclusively vai a factor VII-dependent mechanism. Arthritis Rheum. 2002;46:2857–66.
Knijff-Dutmer EA, Koerts J, Nieuwland R, Kalsbeek-Batenburg EM, van de Laar MA. Elevated levels of platelet microparticles are associated with disease activity in rheumatoid arthritis. Arthritis Rheum. 2002;46:1498–503.
Hidaka T, Suzuki K, Matsuki Y, Takamizawa-Matsumoto M, Kataharada K, Ishizuka T, et al. Filtration leukocytapheresis therapy in rheumatoid arthritis: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 1999;42:431–7.
Emmrich J, Petermann S, Nowak D, Beutner I, Brock P, Klingel R, et al. Leukocytapheresis (LCAP) in the management of chronic active ulcerative colitis—results of a randomized pilot trial. Dig Dis Sci. 2007;52:2044–53.
Ueki Y, Yamasaki S, Kanamoto Y, Kawazu T, Yano M, Matsumoto K, et al. Evaluation of filtration leucocytapheresis for use in the treatment of patients with rheumatoid arthritis. Rheumatology (Oxford). 2000;39:165–71.
Eguchi K, Saito K, Kondo M, Hidaka T, Ueki Y, Tanaka Y. Enhanced effect of high-dose leukocytapheresis using a large filter in rheumatoid arthritis. Mod Rheumatol. 2007;17:481–5.
Hidaka T, Suzuki K. The mechanism of the efficiency of leukocytapheresis on rheumatoid arthritis. Ther Apher. 1997;1:215–8.
Hidaka T, Suzuki K, Matsuki Y, Takamizawa-Matsumoto M, Okada M, Ishizuka T, et al. Changes in CD4+ T lymphocyte subsets in circulating blood and synovial fluid following filtration leukocytapheresis therapy in patients with rheumatoid arthritis. Ther Apher. 1999;3:178–85.
Ueki Y, Nakamura H, Kanamoto Y, Miyazaki M, Yano M, Matsumoto K, et al. Comparison of lymphocyte depletion and clinical effectiveness on filtration leukocytapheresis in patients with rheumatoid arthritis. Ther Apher. 2001;5:455–61.
Hidaka T, Suzuki K, Kawakami M, Okada M, Kataharada K, Shinohara T, et al. Dynamic changes in cytokine levels in serum and synovial fluid following filtration leukocytapheresis therapy in patients with rheumatoid arthritis. J Clin Apher. 2001;16:74–81.
Andoh A, Ogawa A, Kitamura K, Inatomi O, Fujino S, Tsujikawa T, et al. Suppression of interleukin-1beta- and tumor necrosis factor-alpha-induced inflammatory responses by leukocytapheresis therapy in patients with ulcerative colitis. J Gastroenterol. 2004;39:1150–7.
Hanai H, Iida T, Takeuchi K, Watanabe F, Maruyama Y, Kikuyama M, et al. Decrease of reactive-oxygen-producing granulocytes and release of IL-10 into the peripheral blood following leukocytapheresis in patients with active ulcerative colitis. World J Gastroenterol. 2005;11:3085–90.
Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31:315–24.
Prevoo ML, van’t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include 28-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995;38:44–8.
Jy W, Horstman LL, Jimenez JJ, Ahn YS, Biro E, Nieuwland R, et al. Measuring circulating cell-derived microparticles. J Thromb Haemost. 2004;2:1842–51.
Zarbock A, Polanowska-Grabowska RK, Ley K. Platelet–neutrophil-interactions: linking hemostasis and inflammation. Blood Rev. 2007;21:99–111.
Bergmeier W, Chauhan AK, Wagner DD. Glycoprotein Ibalpha and von Willebrand factor in primary platelet adhesion and thrombus formation: lessons from mutant mice. Thromb Haemost. 2008;99:264–70.
Hutchinson RM, Davis P, Jayson MI. Thrombocytosis in rheumatoid arthritis. Ann Rheum Dis. 1976;35:138–42.
Farr M, Scott DL, Constable TJ, Hawker RJ, Hawkins CF, Stuart J. Thrombocytosis of active rheumatoid disease. Ann Rheum Dis. 1983;42:545–9.
Fukunaga K, Fukuda Y, Yokoyama Y, Ohnishi K, Kusaka T, Kosaka T, et al. Activated platelets as a possible early marker to predict clinical efficacy of leukocytapheresis in severe ulcerative colitis patients. J Gastroenterol. 2006;41:524–32.
Yagi Y, Andoh A, Inatomi O, Bamba S, Tsujikawa T, Fujiyama Y, et al. Modulation of platelet aggregation responses by leukocytapheresis therapy in patients with active ulcerative colitis. J Gastroenterol. 2006;41:540–6.
Gasser O, Hess C, Miot S, Deon C, Sanchez JC, Schifferli JA. Characterisation and properties of ectosomes released by human polymorphonuclear neutrophils. Exp Cell Res. 2003;285:243–57.
Hirayama A, Nagase S, Ueda A, Ishizu T, Taru Y, Yoh K, et al. Oxidative stress during leukocyte absorption apheresis. J Clin Apher. 2003;18:61–6.
Daniel L, Fakhouri F, Joly D, Mouthon L, Nusbaum P, Grunfeld JP, et al. Increase of circulating neutrophil and platelet microparticles during acute vasculitis and hemodialysis. Kidney Int. 2006;69:1416–23.
Gasser O, Schifferli JA. Activated polymorphonuclear neutrophils disseminate anti-inflammatory microparticles by ectocytosis. Blood. 2004;104:2543–8.
Hoffmann PR, de Cathelineau AM, Ogden CA, Leverrier Y, Bratton DL, Daleke DL, et al. Phosphatidylserine (PS) induces PS receptor-mediated macropinocytosis and promotes clearance of apoptotic cells. J Cell Biol. 2001;155:649–59.
Acknowledgments
We thank Drs. Y. Aratake, Y. Ogata, I. Kobayashi, and S. Shakano (University of Miyazaki) for their technical assistance.
Conflict of interest statement
None.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Umekita, K., Hidaka, T., Ueno, S. et al. Leukocytapheresis (LCAP) decreases the level of platelet-derived microparticles (MPs) and increases the level of granulocytes-derived MPs: a possible connection with the effect of LCAP on rheumatoid arthritis. Mod Rheumatol 19, 265–272 (2009). https://doi.org/10.1007/s10165-009-0164-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10165-009-0164-2