Effects of proinflammatory mediators on canine neutrophil chemotaxis and aggregation.
The present study investigated in vitro the qualitative and quantitative neutrophil function-activating properties of the most important non-cytokine participants in the acute inflammatory cell response. Apart from the results obtained with leukotriene (LT) D4, similar qualitative relationships were found for the several mediators tested regarding effects on neutrophil migration and aggregation. Thus, LTB4, PAF-acether and zymosan-activated serum all activated both functions, while f-Met-Leu-Phe had no effect. In all cases, the half-maximal eliciting concentration (EC50) for induction of chemotaxis was much lower than for aggregation, indicating that high and low receptor affinity responses were being studied, respectively. LTD4 induced modest aggregation, but was virtually without effect on migration. Using PAF-acether as stimulus, the mechanism of aggregation was studied in more detail. The results indicate that LTB4, PAF-acether, the complement-split products C5a/C5a desArg, and perhaps LTD4, may play a role as stimulants of neutrophil functions in inflammatory processes in vivo.
Department of Pharmacology, Leo Pharmaceutical Products, Ballerup, Denmark.
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Strøm
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Thomsen
D000704:Analysis of Variance; D000818:Animals; D002449:Cell Aggregation / Q000187:drug effects*; D002630:Chemotactic Factors / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D015937:Complement C5a, des-Arginine / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000276:immunology; D015289:Leukotrienes / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects; D010972:Platelet Activating Factor / Q000494:pharmacology
D002630:Chemotactic Factors; D015937:Complement C5a, des-Arginine; D015289:Leukotrienes; D010972:Platelet Activating Factor; D009240:N-Formylmethionine Leucyl-Phenylalanine