SEQUENTIAL POTENTIATION AND INHIBITION OF PMN REACTIVITY BY MAXIMALLYSTIMULATED PLATELETS

In a recent study, we showed that granulocyte-macrophage colony-stimul ating factor (GM-CSF) and supernatants from partially stimulated plate lets undergoing selective alpha-granule release synergistically enhanc ed polymorphonuclear leukocyte (PMN) response to N-formyl-methionyl-le ucyl-phenylalanine (fMLP). The active factor released from platelet al pha-granules was identified as platelet factor four (PF4). In this stu dy we investigate the joint effect on PMN reactivity of GM-CSF and sup ernatants from platelets maximally stimulated to release both alpha- a nd dense granule contents, These platelet supernatants enhanced PMN ch emiluminescence (CL; a measure of the oxidative burst) during short in cubations, whereas longer incubations led to the loss of this enhancem ent and the prevention of PMN priming by GM-CSF The platelet-derived i nhibitory factor was of low molecular weight, originated from the dens e granule precursor(s), and its generation required the presence of PM N, When ATP/ADP were incubated with PMN at concentrations found in pla telet-dense granules, they produced a similar biphasic effect on PMN r eactivity (a potentiation followed by inhibition) as seen with the pla telet supernatants, The inhibitory effect of these nucleotides coincid ed with their conversion to AMP. AMP per se had an immediate inhibitor y effect on PMN response to fMLP and prevented PMN priming by GM-CSF. This study confirms that partially stimulated platelets enhance PMN re activity. However, during maximal stimulation, nucleotides released fr om the platelet-dense granules are converted to AMP which in turn can counteract the PMN priming effects of factors such as PF4 and GM-CSF.