Cytokines, glucocorticoids and lipocortins in the control of neutrophil migration.
By using a simple murine air-pouch technique we were able to measure an intense neutrophil infiltration in response to the local application of specific pro-inflammatory stimuli such as interleukin-1 and interleukin-8. The role of endogenous and exogenous lipocortin 1 on this cellular migratory response was evaluated. Exogenously i.v. administration of human recombinant lipocortin 1 and its N-terminus peptide Ac2-26 dose-dependently inhibited IL-1-induced neutrophil migration with calculated ED50 values of 5.18 +/- 0.74 micrograms and of 88.0 +/- 13.1 micrograms per mouse, respectively. Direct injection of these agents into the pouch was ineffective. In keeping with these observations, the inhibitory action exerted by dexamethasone, in both IL-1- and IL-8-induced cell infiltration, was abrogated by passive immunisation of mice with specific anti-lipocortin 1 antibodies. In conclusion, lipocortin 1 is not only a mediator of some of the anti-inflammatory actions of glucocorticoid hormones, but can also modulate the effect that specific cytokines have on the trafficking of highly specialised cells like the neutrophils.
Department of Biochemical Pharmacology, William Harvey Research Institute, Medical College of St. Bartholomew's Hospital, London, UK.
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Perretti
R J
RJ
Flower
D000818:Animals; D017305:Annexin A1 / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology
D017305:Annexin A1; D005938:Glucocorticoids; D007375:Interleukin-1; D016209:Interleukin-8