ROLE OF GPIIB-IIIA IN PLATELET-MONOCYTE AND PLATELET-NEUTROPHIL CONJUGATE FORMATION IN WHOLE-BLOOD

Platelets in stirred whole blood can be induced to form aggregates and also to form heterotypic platelet-monocyte (PIM) and platelet-neutrop hil (P/N) conjugates, Here we have investigated the effects of three G PIIb-IIIa antagonists (GR144053F, MK-852 and Reopro(TM), a CD62P-block ing antibody, GA6, and EDTA on the conjugate formation that occurs on stirring whole blood and in response to adding ADP and PAF, We have co nfirmed the identities of the conjugates by light microscopy after cel l sorting. Platelet aggregation was measured by platelet counting, Mon ocytes, neutrophils, Prm and P/N were detected and quantitated using i mmunofluorescence and flow cytometry, Stirring whole blood resulted in both platelet aggregation and formation of P/M but not P/N. Adding AD P or PAF to whole blood caused rapid platelet aggregation and generati on of both P/M and P/N, All of the GPIIb-IIIa antagonists studied had similar effects: inhibition of stirring-induced platelet aggregation a nd P/M formation, and inhibition of ADP-induced platelet aggregation a nd P/N formation, In contrast, they accelerated ADP induced-P/M conjug ate formation and PAF-induced formation of both P/M and P/N, Both EDTA and GA6 completely inhibited P/M and P/N, which is commensurate with CD62P being involved in platelet-leucocyte conjugate formation. The re sults of these investigations suggest that GPIIb-IIIa has a dual role in determining the interaction between platelets and leukocytes.