In-vivo blockage of neutrophil migration by LPS is mimicked by a factor released from LPS-stimulated macrophages.
The present study was performed to determine the effect of an intravenous injection of the macrophage-derived neutrophil chemotactic factor (MNCF) (Cunha & Ferreira 1986) on neutrophil migration to rat peritoneal cavities, which were challenged with chemotactic stimuli. Macrophage monolayers stimulated by LPS release a factor (MW greater than 10,000 D) which, when injected intravenously, blocked neutrophil migration in carrageenin-induced peritonitis. This inhibition was dependent on dose and lasted more than 2 h. It was not due to neutropaenia, hypotension or LPS contamination. Neutrophil migration induced by LPS, MNCF, the Gram-negative bacterium Pseudomonas aeruginosa was also blocked by intravenous administration of the factor. Intravenous injection of recombinant interleukin 1 beta or tumour necrosis factor-alpha, present in the samples of the factor, failed to reproduce the described inhibitory effect on neutrophil migration. The release of this factor by LPS-stimulated macrophage monolayers was inhibited by dexamethasone but not by indomethacin. It is suggested that the failure of neutrophils to migrate during septicaemia may be the result of a continuous release of chemotactic factors in the circulation, particularly of the macrophage-derived neutrophil chemotactic factor(s).
Cunha
F Q
FQ
Department of Pharmacology, Faculty of Medicine, University of Säo Paulo, Campus Ribeiräo Preto, Brazil.
Souza
G E
GE
Souza
C A
CA
Cerqueira
B C
BC
Ferreira
S H
SH
D000818:Animals; D002630:Chemotactic Factors / Q000008:administration & dosage / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D007275:Injections, Intravenous; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D011112:Polymyxin B / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D002630:Chemotactic Factors; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D011112:Polymyxin B