Expression of complement components and inhibitors on platelet microparticles.
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.
Yin
Wei
W
Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY, USA.
Ghebrehiwet
Berhane
B
Peerschke
Ellinor I B
EI
D000911:Antibodies, Monoclonal / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D018958:CD55 Antigens / Q000378:metabolism; D018957:CD59 Antigens / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D003167:Complement Activation; D050718:Complement C1 Inhibitor Protein / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D024101:Mitochondrial Proteins / Q000378:metabolism
D000911:Antibodies, Monoclonal; C087299:C1QBP protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D002352:Carrier Proteins; D050718:Complement C1 Inhibitor Protein; D007476:Ionophores; D024101:Mitochondrial Proteins; D000001:Calcimycin; D003165:Complement System Proteins