Regulation of polymorphonuclear leukocyte function by platelets

ABSTRACT

To investigate the full effect of platelet-derived constituents on various polymorphonuclear neutrophil leukocyte responses. Polymorphonuclear neutrophil leukocytes and platelets were separated from fresh blood of normal healthy volunteers. Platelets were then stimulated partially, or maximally to release constituents of their a- or a- and dense granules. The effects of these constituents on polymorphonuclear neutrophil leukocyte function [oxidase activity, degranulation and migration] were investigated. Platelet-derived constituents were found to both enhance, and inhibit polymorphonuclear neutrophil leukocytes-oxidant production, depending on the incubation time. Enhancement was due to dense granule-derived nucleotides [adenosine diphosphate and adenosine diphosphate], while inhibition was due to adenosine monophosphate derived from these nucleotides by polymorphonuclear neutrophil leukocyte surface nucleotidases. This latter inhibitory effect was reversed by the cytokine, granulocyte-macrophage colony stimulating-factor. Moreover, platelet constituents consistently enhanced other polymorphonuclear neutrophil leukocyte responses including degranulation and migration regardless of the incubation period. The latter enhancement was due to a-granule constituents, most likely platelet factor 4. Platelets, through release of their granular constituents, are able to modulate polymorphonuclear neutrophil leukocyte function in a way that is physiologically beneficial