The release of a neutrophil chemotactic factor from peritoneal macrophages by endotoxin: inhibition by glucocorticoids.
Glucocorticoids inhibit the migration of neutrophils induced by endotoxin (E. coli lipopolysaccharide, LPS) in vivo. Macrophage monolayers stimulated by LPS showed a dose-dependent release into the supernatant of a chemotactic factor for neutrophils, MNCF, which was active in vivo and in vitro. Dexamethasone reduced the neutrophil migration into the abdominal cavities of rats that was induced by LPS, but did not affect the migration induced by MNCF. The release of MNCF by LPS-pretreated macrophage monolayers was inhibited by dexamethasone and hydrocortisone but not by indomethacin and BW755C. MNCF was stable at 56 degrees C and did not release histamine from mast cells. Thus, MNCF activity seems not to be due to arachidonic acid metabolites or C5/C5a. MNCF shares some properties with interleukin-I, such as the blockade of its release by glucocorticoids, the association of its activity with a material of a molecular weight greater than 10 000 Daltons and the abolition of its activity by incubation with phenylglyoxal. However MNCF liberation was not blocked by cycloheximide and the time course of its release by macrophage monolayers stimulated by LPS differed from that described for interleukin-1. In addition human interleukin-1 when tested in dexamethasone-treated test rats failed to induce neutrophil migration. It is suggested that inhibition by glucocorticoids of LPS-induced neutrophil migration in vivo is not due to a direct effect upon the migrating cells but rather to an indirect one, i.e. through blockade of MNCF release by macrophages.
D000818:Animals; D002630:Chemotactic Factors / Q000378:metabolism*; D004731:Endotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010658:Phenylglyoxal / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013696:Temperature
D002630:Chemotactic Factors; D004731:Endotoxins; D005938:Glucocorticoids; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D010658:Phenylglyoxal