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.
Perretti
M
M
Department of Biochemical Pharmacology, William Harvey Research Institute, Medical College of St. Bartholomew's Hospital, London, UK.
Flower
R J
RJ
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