Summary
Platelet recruitment crucially depends on amplification systems provided by autocrine
and paracrine factors such as adenosine diphosphate. In inflammatory states, consumption
of coagulation proteins, such as antithrombin aggravates the procoagulant state. In
this study, we report that platelets express synde-can-4, an antithrombin-binding
cell surface heparan sulphate proteoglycan, whose ligation with antithrombin inhibits
activated platelet-dependent superoxide anion release from neut-rophils by the limitation
of adenosine diphosphate and adeno-sine triphosphate secretion in activated platelets.
Adenosine triphosphate-induced platelet aggregation is reduced after treatment of
platelets with antithrombin, which is reversed by blockade of syndecan-4. We further
observed that antithrombin limits CD40 ligand expression in adenosine diphosphate-activated
platelets and inhibits the shedding of syndecan-4 from activated platelets. Syndecan-4
appears to be directly involved in regulating platelet aggregation as anti-syndecan-4
antibody augments platelet aggregation. We suggest that antithrombin might exert beneficial
effects in disseminated intravascular coagulation by reducing platelet activation,
observed as inhibited CD40 ligand expression, syndecan-4 shedding, and adenosine diphosphate-
and adenosine triphosphate-release from activated platelets with subsequent inhibition
of neutrophil respiratory burst. From these data it is concluded that syndecan-4 may
play important roles in the regulation of inflammatory effects of platelets.
Keywords
Cell-cell interactions - disseminated intravascular coagulation (DIC) / sepsis - antithrombin
- heparins / glycosaminoglycans - platelet pharmacology
