Migratory responses of ovine neutrophils to inflammatory mediators in vitro and in vivo.
The migration of 111In-labeled ovine neutrophils towards a range of inflammatory mediators was examined in vitro using a 48-well chemotaxis chamber. Typical curves were obtained for the chemotactic response to zymosan-activated plasma (ZAP, a source of C5a) and interleukin-8 (IL-8). In contrast, leukotriene B4 (LTB4), platelet-activating factor (PAF), interleukin-1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF-alpha), N-formyl-methionine-leucyl-phenylalanine (fMLP), and endotoxins from Escherichia coli and Pseudomonas aeruginosa failed to induce neutrophil migration in vitro. Of these mediators LTB4, ZAP, IL-1 alpha, TNF-alpha, IFN-gamma, and IL-8 have been reported to induce neutrophil accumulation in skin of sheep, and in the current study E. coli endotoxin was a potent inducer of 111In-labeled neutrophil accumulation and plasma leakage in skin. In contrast, PAF induced intense plasma leakage but failed to induce accumulation of 111In-labeled neutrophils in skin. Histologic examination of skin sites receiving PAF confirmed the failure of PAF to stimulate neutrophil extravasation. FMLP lacked inflammatory activity in skin. Coinjection of actinomycin D did not abrogate recruitment of neutrophils to skin sites receiving LTB4; thus neither induction of endothelial adhesion molecules nor synthesis of IL-8 was necessary for LTB4 to exhibit inflammatory activity in vivo.
CSIRO Division of Animal Health, Armidale, Australia.
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Mulder
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Colditz
D000818:Animals; D002465:Cell Movement; D002630:Chemotactic Factors / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D015936:Complement C5a / Q000494:pharmacology; D005260:Female; D016209:Interleukin-8 / Q000494:pharmacology; D007975:Leukotriene B4 / Q000494:pharmacology; D008853:Microscopy; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology*; D010972:Platelet Activating Factor / Q000494:pharmacology; D012756:Sheep; D012867:Skin / Q000033:anatomy & histology / Q000187:drug effects; D013051:Spectrometry, Gamma
D002630:Chemotactic Factors; D016209:Interleukin-8; D010972:Platelet Activating Factor; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a