Release of oxygen metabolites from chemoattractant-stimulated neutrophils is inhibited by resting platelets: role of extracellular adenosine and actin polymerization

摘要: The effect of human platelets on chemoattractant-induced generation oxygen metabolites in neutrophils was investigated, using luminol- enhanced chemiluminescence (CL). Resting inhibited the extracellular, but not intracellular, production radicals formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe)-stimulated neutrophils. Maximal obtained at physiological neutrophil/platelet ratio 1/50. Similar results were acquired by adding supernatants platelets, indicating a role for soluble factor. Removal extracellular adenosine deaminase (ADA), or blocking adenosine-receptors theophylline, antagonized inhibitory effects (or equivalent supernatant) neutrophil respiratory burst. In contrast, accumulation apyrase inhibition. Exogenous mimicked fMet-Leu-Phe-induced To further assess platelet-derived adenosine, fixed with paraformaldehyde. We found that as well their supernatant, fMet- Leu-Phe-induced CL-response to same extent viable cells. These also reversed ADA and respectively. A prior removal platelet suspension ADA, followed treatment erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA) inactivate did reverse action However, if receptors time blocked theophyline, inhibition significantly reduced. Platelets markedly increased suspension. S-(4-Nitrobenzyl)-6- thioguanosine (NBTG), unaffected alpha, beta-methyl- eneadenosine5′diphosphate (AMP-CP), platelet- dependent is due an release endogenous from degradation AMP. correlation, NBTG, AMP-CP, platelet-mediated Consequently, these data suggest factor increases endogenously formed neutrophils, terminating radicals. oxidase activity associated induced polymerization actin margin Treatment cytochalasin B both F-actin content CL-response. summary, resting limit chemoattractant- stimulated thus preventing excessive damage host tissues vascular space. This suggested be increase neutrophil-derived enhancing autoregulatory pathway, peripheral filaments forming barrier reactive