Platelets prime PMN via released PF4: mechanism of priming and synergy with GM‐CSF

KA Aziz, JC Cawley, M Zdzel - British journal of haematology, 1995 - Wiley Online Library
KA Aziz, JC Cawley, M Zdzel
British journal of haematology, 1995Wiley Online Library
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 pathophysiologi‐
cally important, mechanism by which platelets can enhance PMN reactivity. We first
observed that addition of platelets to PMN suspensions enhanced the chemilumines‐cence
response of PMN to FMLP. This enhancement occurred without augmentation of superoxide …
Summary
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 pathophysiologi‐cally important, mechanism by which platelets can enhance PMN reactivity. We first observed that addition of platelets to PMN suspensions enhanced the chemilumines‐cence 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 α‐granules. The α‐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.
Wiley Online Library