In this study we have investigated the effect of human mononuclear leu
kocytes (ML) on platelet aggregation. The results obtained demonstrate
d that coincubation of platelets with nonstimulated ML decreased plate
let aggregation induced by collagen or thrombin in a concentration-dep
endent manner. The inhibitory effect increased with the incubation per
iod of the cells, reaching a plateau at 5 minutes. T and non-T enriche
d ML suspensions exerted an inhibitory effect similar to the total pop
ulation of ML. Supernatants from ML or mixed cell suspensions also dim
inished platelet aggregation. 6-keto PGFl alpha concentration in the s
upernatants was less than 10 pg/ml. Hemoglobin, L-arginine and cytochr
ome C did not modify the antiaggregating activity of ML, whereas super
oxide dismutase potentiated the inhibition of aggregation mediated by
ML. The inhibitory effect was not modified by monoclonal antibody (MoA
b) against the lymphocyte function-associated antigen 1, alpha subunit
(LFA-1 alpha) or by a MoAb directed against P-selectin. Our results d
emonstrated that ML inhibited platelet aggregation, at least partially
, by the release of a soluble factor(s) distinct of prostacyclin or ni
tric oxide. Surface adhesion molecules seem also not to be involved.