Platelets as inhibitory cells in neutrophil-mediated cytolysis.
Neutrophilic polymorphonuclear leukocytes (PMNs), triggered by opsonized zymosan (OPZ), lysed chicken red blood cells as measured by a chromium 51 release method. The lysis was prevented by scavengers of hypochlorous acid. When platelets were added to the cytolytic system, a dose-dependent inhibition of the lysis was observed. Moreover, platelets lowered the HOCl recovery from OPZ-triggered PMNs. A positive linear relationship was found between the extent of the lysis mediated by and the amount of HOCl recovered from PMNs. Finally, both the inhibition of the lysis and the reduction of the HOCl recovery induced by platelets were prevented by pulsing platelets with carmustine (BCNU) to block their glutathione cycle. These results suggest that platelets act by consuming via their glutathione cycle significant amounts of PMN-derived hydrogen peroxide, with a consequent impairment of the PMN HOCl production and, in turn, lytic efficiency. Consistent with such a conclusion, platelets were found to consume PMN-derived H2O2 via a BCNU-inhibitable process. Further, the platelet inhibitory activity could be abolished by the addition of an appropriate extra-flux of enzymatically generated H2O2. No evidence for a platelet-induced inhibition of OPZ-PMN interaction, PMN myeloperoxidase release, and H2O2 production was obtained. The present study provides direct evidence for a platelet-dependent mechanism capable of controlling the PMN production of highly reactive oxidants and, in turn, the PMN cytolytic activity.
Dallegri
F
F
First Medical Clinic, University of Genoa Medical School, Italy.
Ballestrero
A
A
Ottonello
L
L
Patrone
F
F
D000210:Acute-Phase Reaction / Q000276:immunology; D000818:Animals; D001792:Blood Platelets / Q000201:enzymology / Q000276:immunology*; D002374:Catalase / Q000037:antagonists & inhibitors; D002645:Chickens; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors; D006461:Hemolysis; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis
D002374:Catalase; D005980:Glutathione Reductase