Interleukin-1 beta primes interleukin-8-stimulated chemotaxis and elastase release in human neutrophils via its type I receptor.
Interleukin-1 (IL-1) is a pleiotropic proinflammatory cytokine which binds to human neutrophils (PMN) and can directly or indirectly activate their functions. In this study we show that a brief exposure to IL-1 beta induces a potentiation of both PMN elastase release and chemotactic response to interleukin-8 (IL-8), the prototype of C-X-C chemokines. Priming by IL-1 beta was maximal at 100 ng/ml, was completely blocked in the presence of IL-1 receptor antagonist (IL-1ra) and, in the chemotaxis assay, was best observed at suboptimal (3-6 ng/ml) or inactive (0.75 ng/ml) concentrations of IL-8. Priming of PMN by IL-1 beta was completely blocked by M1, a specific antibody against the type I IL-1 receptor (IL-1RI). On the other hand M22, an antibody directed against the IL-1 decoy type II IL-1 receptor did not affect IL-1 beta action and slightly increased the priming effect. Thus, exclusively via its type I receptor, IL-1 beta can act on PMN at multiple levels, by promoting their accumulation in tissues through the induction of chemotactic factors (e.g. IL-8) and the upregulation of adhesion molecules, and by priming their response to chemotactic agonists.
Brandolini
L
L
Dompé S.p.A. Research Center, L'Aquila, Italy.
Sergi
R
R
Caselli
G
G
Boraschi
D
D
Locati
M
M
Sozzani
S
S
Bertini
R
R
D019138:Antibodies, Blocking / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000502:physiology; D004357:Drug Synergism; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D016209:Interleukin-8 / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D019272:Leukocyte Elastase / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology*; D017472:Receptors, Interleukin-1 / Q000502:physiology*; D053573:Receptors, Interleukin-1 Type I
D019138:Antibodies, Blocking; D007375:Interleukin-1; D016209:Interleukin-8; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D019272:Leukocyte Elastase