The Stimulatory Effect of Platelets and Platelet Membranes on the Procoagulant Activity of Leukocytes

Abstract

A B S T R A C T Leukocytes can generate procoagulant (tissue factor) activity when incubated with endotoxin. These studies were undertaken to determine whether platelets could influence the procoagulant activity generated by leukocytes. Intact or disrupted platelets (rabbit or human) enhanced the clot-promoting properties of rabbit leukocytes.The enhancing effect of human platelets on human leukocytes required the presence of human serum (devoid of factor VII and X activities). When platelets were incubated with endotoxin in the absence of leukocytes, no increase in their clot-promoting properties was discernible. However, a mixture of platelets, leukocytes, and endotoxin generated procoagulant activity which appeared rapidly and was fivefold greater than that produced by leukocytes incubated with endotoxin alone. The enhancement produced by platelets was even more pronounced if homogenates were used. The platelet effect was examined in more detail by the substitution of membranes, granules, and the "soluble" fraction for whole platelets in the test system. The stimulating activity was localized to the particulate fractions, i.e., membranes and granules. Prior treatment of platelet membranes with phospholipase C or gangliosides or by extraction of lipid resulted in loss of enhancing activity, whereas no inhibition was observed after exposure to neuraminidase or trypsin. It is proposed that platelets contribute a membrane lipoprotein surface which enhances the procoagulant activity generated by leukocytes in the presence of endotoxin. This mechanism may be involved in some of the clinical and pathologic manifestations of gram-negative sepsis with disseminated intravascular coagulation.

Enhancement of mononuclear procoagulant activity by platelet 12-hydroxyeicosatetraenoic acid.

“…2, MN + E). In control experiments (data not shown), we confirmed previously reported results that platelets did not generate TFa in the absence of leukocytes (15).…”

“…The platelet contribution is complex and can be summarized as follows: (a) platelets and platelet membranes enhance endotoxin-induced TFa, (b) platelets alone induce TFa, and (c) platelet cytosol stimulates development of a procoagulant activity that is not TFa (15). The (Table I), Among a series of fatty acids, the enhancing effect was only observed with arachidonic acid and occurred in a dose-dependent manner (Fig.…”

“…The platelet is another blood component known to be involved in the induction-modulation of TFa (13)(14)(15). The platelet contribution is complex and can be summarized as follows: (a) platelets and platelet membranes enhance endotoxin-induced TFa, (b) platelets alone induce TFa, and (c) platelet cytosol stimulates development of a procoagulant activity that is not TFa (15).…”

C5 chemotactic fragment induces leukocyte production of tissue factor activity: a link between complement and coagulation.

“…Leukocytes from human blood were prepared after sedimentation with dextran, by the method of Boyum as described (6). Platelet-rich plasma was prepared as previously described (6).…”

“…Leukocytes can be induced to generate tissue factor activity by incubation with bacterial endotoxin, phytohemagglutinin, antigen-antibody complexes, platelets, and renal dialysis membranes (4)(5)(6)(7).…”