Platelets prime PMN via released PF4: mechanism of priming and synergy with GM-CSF.
Platelet-PMN interactions have been extensively studied and a spectrum of possible effects has been demonstrated. However, the physiological relevance of many of the observed in vitro phenomena remains obscure. Here we report a novel, and potentially pathophysiologically important, mechanism by which platelets can enhance PMN reactivity. We first observed that addition of platelets to PMN suspensions enhanced the chemiluminescence response of PMN to FMLP. This enhancement occurred without augmentation of superoxide generation and did not involve mutual platelet-PMN adhesion. The soluble material responsible was biochemically and immunologically identified as PF4 derived from platelet alpha-granules. The alpha-granule release was shown to be selective and required minimal platelet stimulation. Since the PF4 effect did not influence NADPH oxidase activation, it differed markedly from that of other priming agents such as GM-CSF. Further studies showed that the PF4 effect was attributable entirely to the surface translocation and secretion of primary granule myeloperoxidase. There was marked synergy between PF4 and GM-CSF and both were required for maximal potentiation of PMN reactivity. These results demonstrate that PF4 and GM-CSF employ different pathways in PMN priming. The ease with which platelets could release PF4 at sites of vessel-wall damage and inflammation suggests that platelet-PMN interaction via PF4 is likely to be of major pathophysiological importance.
Department of Haematology, University of Liverpool.
K A
KA
Aziz
J C
JC
Cawley
M
M
Zuzel
D001792:Blood Platelets / Q000502:physiology*; D015550:Cell Degranulation; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D004357:Drug Synergism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006801:Humans; D007163:Immunosorbent Techniques; D008163:Luminescent Measurements; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010101:Oxygen Consumption; D010978:Platelet Factor 4 / Q000302:isolation & purification / Q000502:physiology*
D010978:Platelet Factor 4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor