Leucocyte-dependent platelet activation: an alternative pathway for initiation of blood clotting in inflammation.
Fibrin deposition is a prominent feature of several inflammatory diseases but the extract mechanism(s) leading to fibrinogen-fibrin conversion has not been completely clarified. We describe here a new cellular pathway for initiation of blood clotting resulting from a leucocyte-platelet interaction. Human washed platelet suspensions, free of leucocytes, isolated from whole blood or leucocyte-enriched platelet-rich plasma (PRP) after four hours' incubation with bacterial endotoxin, had strong procoagulant activity (40-100-fold that of control platelets). When platelets were challenged with endotoxin in the absence of white blood cells (i.e. in PRP) the subsequently washed platelets were devoid of procoagulant activity indicating that leucocytes are essential mediators in the development of platelet coagulant activity induced by endotoxin. This property is mostly confined to the mononuclear fraction. 'Stimulated' platelets have the peculiarity that they trigger blood coagulation by activating factor X independently of both the intrinsic and extrinsic pathways. These findings add a new function to circulating mononuclear cells and provide experimental evidence for an unrecognized cellular pathway of fibrin formation in inflammatory diseases.
D001777:Blood Coagulation / Q000187:drug effects; D001779:Blood Coagulation Factors / Q000502:physiology; D001792:Blood Platelets / Q000502:physiology*; D004731:Endotoxins / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000097:blood*; D007962:Leukocytes / Q000502:physiology*
D001779:Blood Coagulation Factors; D004731:Endotoxins