Role of platelets and the arachidonic acid pathway in the regulation of neutrophil oxidase activity.
The intercellular mechanisms involved in platelet-mediated regulation of neutrophil function remain incompletely understood. This study investigated the role of the arachidonic acid pathway in the modulation of chemoattractant-induced production of oxygen metabolites, measured as luminol-amplified chemiluminescence (CL). We demonstrate that platelets dose-dependently inhibit the CL response in neutrophils stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP). Incubation with eicosatetrayonic acid (ETYA), a combined cyclooxygenase and lipooxygenase inhibitor, dramatically decreased the fMLP-induced CL response in neutrophils, an effect that was further enhanced in the presence of platelets. The separate effects of eicosatriyonic acid (ETI) and indomethacin, specific inhibitors of lipoxygenase and cyclooxygenase, respectively, were significantly lower compared to the action of ETYA. On the contrary, impediment of arachidonic acid release with the phospholipase A2 inhibitor arachidonyl trifluoromethyl ketone (ATK) markedly increased the production of oxygen radicals triggered by fMLP. The addition of exogenous arachidonic acid clearly decreased the fMLP-induced CL response in neutrophils, which further strengthens a downregulating effect of arachidonic acid on oxidase activity. This inhibitory action of arachidonic acid, however, was reversed upon co-incubation with platelets. In conclusion, this study suggests that an accumulation of arachidonic acid, following chemotactic peptide stimulation, turns off neutrophil oxidase activity. Furthermore, platelets may support the synthesis of reactive arachidonic acid metabolites, which modulate oxygen radical production in neutrophils.
Herbertsson
H
H
Department of Biomedicine and Surgery, Faculty of Health Sciences, Linköping University, Sweden.
Bengtsson
T
T
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism*; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D002450:Cell Communication / Q000276:immunology; D015777:Eicosanoids / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D010088:Oxidoreductases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000276:immunology
D015777:Eicosanoids; D017382:Reactive Oxygen Species; D015117:5,8,11,14-Eicosatetraynoic Acid; D016718:Arachidonic Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010088:Oxidoreductases