title: Platelets enhance Fc(gamma) receptor-mediated phagocytosis and respiratory burst in neutrophils: the role of purinergic modulation and actin polymerization.
abstract: The interaction of platelets with neutrophil granulocytes is considered to play an important role in the inflammatory process, and the present study was focused on platelet-induced modulation of Fcgamma receptor-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 particles, were potentiated by platelets and that maximal enhancement was achieved at a physiological neutrophil/platelet ratio of about 1:50 to 1:100. Platelets both increased the intra- and extracellular generation of oxygen radicals as well as the release of myeloperoxidase from stimulated neutrophils. The presence of platelets also induced a cortical actin polymerization in neutrophils, which might explain the increased phagocytic capacity. Platelets appear to affect neutrophil function in a contact-independent manner that most likely involves ATP, indicated by the following: (1) platelet supernatants, but not fixed platelets, affected neutrophil function in the same way as viable platelets; (2) platelets raised the extracellular ATP level four- to fivefold; (3) exogenous ATP mimicked the effects of platelets on actin polymerization, phagocytosis, and the respiratory burst in neutrophils; (4) hydrolysis of extracellular ATP with apyrase or blocking of ATP receptors with suramin reversed the platelet-induced enhancement of neutrophil function. An increased accumulation of extracellular adenosine, induced by inhibiting endogenous adenosine deaminase or adding exogenous adenosine, reversed the effects of platelets. The platelet-induced potentiation of the respiratory burst was inhibited by the tyrosine kinase inhibitor genistein, suggesting that tyrosine phosphorylation is involved. However, platelets did not significantly affect the Fcgamma receptor-triggered calcium response in neutrophils. In conclusion, we show that platelets, through an ATP-dependent mechanism, potentiate IgG-mediated ingestion and production of oxygen metabolites in neutrophils.
authors.affiliation: Department of Medical Microbiology, Faculty of Health Sciences, Linköping University, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Zalavary
authors.forename: M
authors.initials: M
authors.lastname: Grenegård
authors.forename: O
authors.initials: O
authors.lastname: Stendahl
authors.forename: T
authors.initials: T
authors.lastname: Bengtsson
mesh_terms: D000199:Actins / Q000097:blood; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000097:blood* / Q000494:pharmacology*; D001081:Apyrase / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology*; D002118:Calcium / Q000097:blood; D002450:Cell Communication; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008163:Luminescent Measurements; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D009195:Peroxidase / Q000097:blood; D010587:Phagocytosis; D017452:Receptors, IgG / Q000502:physiology*; D016897:Respiratory Burst; D012441:Saccharomyces cerevisiae; D013498:Suramin / Q000494:pharmacology
chemical_list: D000199:Actins; D017452:Receptors, IgG; C022571:adenosine 5'-O-(3-thiotriphosphate); D013498:Suramin; D000255:Adenosine Triphosphate; D009195:Peroxidase; D001081:Apyrase; D002118:Calcium