title: Platelet-dependent granulocyte activation in vitro: effect of ticlopidine.
abstract: The presence of platelets or platelet release products is known to augment the injury of endothelial cells caused by stimulated neutrophils (PMN leukocytes). In our in vitro studies, platelet-rich or platelet-poor plasma (PRP or PPP) was placed in one compartment and a PMN suspension in the other of a modified Boyden chamber divided by a dialysis membrane. The addition of the aggregating substance (ADP, collagen) to PRP but not to PPP was followed by PMN activation as shown by enzyme release and O-2 generation. The in vivo treatment with ASA completely prevented the platelets from triggering PMN activation. The in vitro addition of a thromboxane synthetase inhibitor (imidazole 10(-3) M) or a lipoxygenase inhibitor (NDGA 10(-6) M) did not show any effect on platelet-dependent PMN activation, thus suggesting that neither TxA2 nor lipoxygenase by-products are involved. Finally, in vitro and in vivo treatment with ticlopidine blunted the stimulating activity of the platelets on PMN. Our data further support the hypothesis that a sequential platelet-PMN interaction may occur, and that the therapeutic effect of some antiplatelet drugs may be partly due to a protective effect against platelet-dependent PMN-mediated vascular damage.
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D003571:Cytochalasin B / Q000494:pharmacology; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology*; D010974:Platelet Aggregation; D013481:Superoxides / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology*; D013988:Ticlopidine
chemical_list: D013876:Thiophenes; D013481:Superoxides; D003571:Cytochalasin B; D000244:Adenosine Diphosphate; D005966:Glucuronidase; D013988:Ticlopidine