ENHANCED ACTIVATION OF PLATELETS WITH ABNORMAL RELEASE OF RANTES IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION

Besides their role in hemostasis, platelets are involved in inflammato ry and immunological processes, and we hypothezise that platelet activ ation may play an immunopathogenetic role in HIV-1 infection. Blood wa s drawn from 15 controls and 20 HIV-1-infected patients with normal pl atelet counts, classified into groups of non-AIDS and AIDS. Platelet a ctivation was detected using flow cytometry with mAbs against the rele ase markers P-selectin and CD63, mAb against GPIb, and the probe annex in V detecting surface exposure of aminophospholipids. The amount of m icrovesicles was measured using mAb against GPIIIa. Compared to contro ls, blood samples from HIV-1-infected patients showed significantly en hanced levels of microvesicles and activated platelets as detected by their exposure of P-selectin, CD63, and aminophospholipids, as well as reduction in GPIb expression. Increased expression of P-selectin and amounts of microvesicles were most pronounced in advanced clinical and immunological disease. When studying the effect of HIV-1 protease inh ibitor therapy (indinavir) on platelet activation, we found that conco mitant with a profound decrease in plasma viral load, there was a near normalization of several of the parameters reflecting enhanced platel et activation. Finally, we demonstrated that platelets may be an impor tant source of the chemokine RANTES in HIV-1-infected patients. Althou gh both unstimulated and SFLLRN-stimulated platelets from asymptomatic patients had enhanced release of RANTES, platelets from AIDS patients were characterized by markedly enhanced spontaneous, but decreased SF LLRN-stimulated release of this chemokine. Taken together, these resul ts, which demonstrate for the first time increased platelet activation in HIV-1-infected patients with normal platelet counts, may represent a previously unrecognized immunopathogenic factor in HIV-1 infection.