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 inflammatory and immunological processes, and we hypothesize that platelet activation may play an immunopathogenetic role in HIV-1 infection. Blood was drawn from 15 controls and 20 HIV-1-infected patients with normal platelet counts, classified into groups of non-AIDS and AIDS. Platelet activation was detected using flow cytometry with mAbs against the release markers P-selectin and CD63, mAb against GPIb, and the probe annexin V detecting surface exposure of aminophospholipids. The amount of microvesicles was measured using mAb against GPIIIa. Compared to controls, blood samples from HIV-1-infected patients showed significantly enhanced 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 inhibitor therapy (indinavir) on platelet activation, we found that concomitant with a profound decrease in plasma viral load, there was a near normalization of several of the parameters reflecting enhanced platelet activation. Finally, we demonstrated that platelets may be an important source of the chemokine RANTES in HIV-1-infected patients. Although 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 SFLLRN-stimulated release of this chemokine. Taken together, these results, 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.
Holme
P A
PA
Research Institute for Internal Medicine, Medical Department A, The National Hospital, University of Oslo, Norway.
Müller
F
F
Solum
N O
NO
Brosstad
F
F
Frøland
S S
SS
Aukrust
P
P
D019380:Anti-HIV Agents / Q000627:therapeutic use; D015415:Biomarkers; D018946:Chemokine CCL5 / Q000378:metabolism*; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D015539:Platelet Activation / Q000276:immunology*; D019562:Viral Load
D019380:Anti-HIV Agents; D015415:Biomarkers; D018946:Chemokine CCL5