Expression of Complement Components and Inhibitors on Platelet Microparticles

Overview

Journal Platelets

Publisher Informa Healthcare

Specialty Hematology

Date 2008 Apr 25

PMID 18432523

Citations 35

Authors

Wei Yin

Berhane Ghebrehiwet

Ellinor I B Peerschke

Affiliations

Soon will be listed here.

Abstract

Platelet microparticles (PMP) are released from activated platelets and play an important role in hemostasis, thrombosis and inflammation. Since platelets were recently found to demonstrate an intrinsic capacity for activating both classical and alternative pathways of the complement system, the present study extended these observations to PMP. PMP were generated by treating platelets with 10 microM A23187 (37 degrees C, 5 min). PMP were identified by flow cytometry, based on size, Annexin V binding, and expression of P-selectin and GPIIb (CD41). PMP expressed gC1qR/p33, a multifunctional cellular protein that was recently described to activate the classical complement cascade. PMP also expressed the classical pathway and contact system regulator, C1 inhibitor (C1-INH), as well as CD55 and CD59. Despite C1-INH expression, PMP supported classical pathway C4 activation in the presence of purified C1 and C4. Moreover, statistically significant deposition of C3b and C5b-9 was detected on PMP exposed to plasma, concurrently with expression of CD55 and CD59. These data provide the first evidence for the ability of PMP to support in situ complement activation. Complement activation contributes to a variety of vascular and inflammatory disease states including atherosclerosis and ischemia/reperfusion injury.

Citing Articles

Immunity and Coagulation in COVID-19.

Avdonin P, Blinova M, Serkova A, Komleva L, Avdonin P Int J Mol Sci. 2024; 25(20).

PMID: 39457048 PMC: 11508857. DOI: 10.3390/ijms252011267.

The role of platelets in central hubs of inflammation: A literature review.

Bo Y, Lu Q, Li B, Sha R, Yu H, Miao C Medicine (Baltimore). 2024; 103(19):e38115.

PMID: 38728509 PMC: 11081549. DOI: 10.1097/MD.0000000000038115.

Complement inhibition can decrease the haemostatic response in a microvascular bleeding model at multiple levels.

Golomingi M, Kohler J, Lamers C, Pouw R, Ricklin D, Dobo J Front Immunol. 2023; 14:1226832.

PMID: 37771595 PMC: 10525698. DOI: 10.3389/fimmu.2023.1226832.

The role of the complement system in kidney glomerular capillary thrombosis.

Yoshida Y, Nishi H Front Immunol. 2022; 13:981375.

PMID: 36189215 PMC: 9515535. DOI: 10.3389/fimmu.2022.981375.

The Role of Platelet-Derived Extracellular Vesicles in Immune-Mediated Thrombosis.

Eustes A, Dayal S Int J Mol Sci. 2022; 23(14).

PMID: 35887184 PMC: 9320310. DOI: 10.3390/ijms23147837.

References

Mause S, von Hundelshausen P, Zernecke A, Koenen R, Weber C . Platelet microparticles: a transcellular delivery system for RANTES promoting monocyte recruitment on endothelium. Arterioscler Thromb Vasc Biol. 2005; 25(7):1512-8. DOI: 10.1161/01.ATV.0000170133.43608.37. View

Gnatenko D, Dunn J, McCorkle S, Weissmann D, Perrotta P, Bahou W . Transcript profiling of human platelets using microarray and serial analysis of gene expression. Blood. 2002; 101(6):2285-93. DOI: 10.1182/blood-2002-09-2797. View

Steinhubl S . Platelets as mediators of inflammation. Hematol Oncol Clin North Am. 2007; 21(1):115-21. DOI: 10.1016/j.hoc.2006.11.015. View

Tans G, Rosing J, Thomassen M, Heeb M, ZWAAL R, Griffin J . Comparison of anticoagulant and procoagulant activities of stimulated platelets and platelet-derived microparticles. Blood. 1991; 77(12):2641-8. View

Vlaicu R, Niculescu F, Rus H, Cristea A . Immunohistochemical localization of the terminal C5b-9 complement complex in human aortic fibrous plaque. Atherosclerosis. 1985; 57(2-3):163-77. DOI: 10.1016/0021-9150(85)90030-9. View

Gawaz M, Ott I, Reininger A, Heinzmann U, Neumann F . Agglutination of isolated platelet membranes. Arterioscler Thromb Vasc Biol. 1996; 16(5):621-7. DOI: 10.1161/01.atv.16.5.621. View

Martinez M, Tesse A, Zobairi F, Andriantsitohaina R . Shed membrane microparticles from circulating and vascular cells in regulating vascular function. Am J Physiol Heart Circ Physiol. 2005; 288(3):H1004-9. DOI: 10.1152/ajpheart.00842.2004. View

Niculescu F, Rus H . Complement activation and atherosclerosis. Mol Immunol. 2000; 36(13-14):949-55. DOI: 10.1016/s0161-5890(99)00117-0. View

Rinder C, Rinder H, Smith B, Fitch J, Smith M, Tracey J . Blockade of C5a and C5b-9 generation inhibits leukocyte and platelet activation during extracorporeal circulation. J Clin Invest. 1995; 96(3):1564-72. PMC: 185782. DOI: 10.1172/JCI118195. View

10.

Morel O, Toti F, Hugel B, Freyssinet J . Cellular microparticles: a disseminated storage pool of bioactive vascular effectors. Curr Opin Hematol. 2004; 11(3):156-64. DOI: 10.1097/01.moh.0000131441.10020.87. View

11.

Zeiger F, Stephan S, Hoheisel G, Pfeiffer D, Ruehlmann C, Koksch M . P-Selectin expression, platelet aggregates, and platelet-derived microparticle formation are increased in peripheral arterial disease. Blood Coagul Fibrinolysis. 2001; 11(8):723-8. DOI: 10.1097/00001721-200012000-00005. View

12.

Franchini M, Veneri D, Lippi G . Inflammation and hemostasis: a bidirectional interaction. Clin Lab. 2007; 53(1-2):63-7. View

13.

Markiewski M, Nilsson B, Nilsson Ekdahl K, Mollnes T, Lambris J . Complement and coagulation: strangers or partners in crime?. Trends Immunol. 2007; 28(4):184-92. DOI: 10.1016/j.it.2007.02.006. View

14.

George J, Pickett E, Saucerman S, McEver R, Kunicki T, Kieffer N . Platelet surface glycoproteins. Studies on resting and activated platelets and platelet membrane microparticles in normal subjects, and observations in patients during adult respiratory distress syndrome and cardiac surgery. J Clin Invest. 1986; 78(2):340-8. PMC: 423547. DOI: 10.1172/JCI112582. View

15.

Conde I, Cruz M, Zhang H, Lopez J, Afshar-Kharghan V . Platelet activation leads to activation and propagation of the complement system. J Exp Med. 2005; 201(6):871-9. PMC: 2213112. DOI: 10.1084/jem.20041497. View

16.

Piccin A, Murphy W, Smith O . Circulating microparticles: pathophysiology and clinical implications. Blood Rev. 2006; 21(3):157-71. DOI: 10.1016/j.blre.2006.09.001. View

17.

Peerschke E, Smyth S, Teng E, Dalzell M, Ghebrehiwet B . Human umbilical vein endothelial cells possess binding sites for the globular domain of C1q. J Immunol. 1996; 157(9):4154-8. View

18.

Choudhury A, Chung I, Blann A, Lip G . Elevated platelet microparticle levels in nonvalvular atrial fibrillation: relationship to p-selectin and antithrombotic therapy. Chest. 2007; 131(3):809-815. DOI: 10.1378/chest.06-2039. View

19.

Ghebrehiwet B, Peerschke E . cC1q-R (calreticulin) and gC1q-R/p33: ubiquitously expressed multi-ligand binding cellular proteins involved in inflammation and infection. Mol Immunol. 2004; 41(2-3):173-83. DOI: 10.1016/j.molimm.2004.03.014. View

20.

Barry O, Pratico D, Savani R, FitzGerald G . Modulation of monocyte-endothelial cell interactions by platelet microparticles. J Clin Invest. 1998; 102(1):136-44. PMC: 509075. DOI: 10.1172/JCI2592. View