PLATELETS ENHANCE FC-GAMMA RECEPTOR-MEDIATED PHAGOCYTOSIS AND RESPIRATORY BURST IN NEUTROPHILS - THE ROLE OF PURINERGIC MODULATION AND ACTIN POLYMERIZATION

The intel action of platelets with neutrophil granulocytes is consider ed to play an important role in the inflammatory process, and the pres ent study was focused on pIatelet-induced modulation of Fc gamma recep tor-mediated functions in neutrophils. We found that phagocytosis and the respiratory burst (measured as luminol-enhanced chemiluminescence) , triggered in neutrophils by immunoglobulin G (IgG)-opsonized yeast p articles, were potentiated by platelets and that maximal enhancement w as achieved at a physiological neutrophil/platelet ratio of about 1:50 to 1:100, Platelets both increased the intra- and extracellular gener ation of oxygen radicals as well as the release of myeloperoxidase fro m stimulated neutrophils. The presence of platelets also induced a cor tical actin polymerization ill neutrophils, which might explain the in creased phagocytic capacity. Platelets appear to affect neutrophil fun ction in a contact-independent maturer that most likely involves ATP, indicated by the following: (1) platelet supernatants, but not fixed p latelets, affected neutrophil function in the same way as viable plate lets; (2) platelets raised the extracellular ATP level four- to fivefo ld; (3) exogenous ATP mimicked the effects of platelets on actin polym erization, phagocytosis, and the respiratory burst in neutrophils; (4) hydrolysis of extracellular ATP with apyrase or blocking of ATP recep tors with suramin reversed the platelet-induced enhancement of neutrop hil function, All increased accumulation of extracellular adenosine, i nduced by inhibiting endogenous adenosine deaminase or adding exogenou s adenosine, reversed the effects of platelets, Tile platelet-induced potentiation of the respiratory burst was inhibited by the tyrosine ki nase inhibitor genistein, suggesting that tyrosine phosphorylation is involved. However, platelets did not significantly affect the Fc gamma receptor triggered calcium response in neutrophils, In conclusion, we show that platelets, through an ATP-dependent mechanism, potentiate I gG-mediated ingestion and production of oxygen metabolites in neutroph ils.