Modulation of IL-1, tumor necrosis factor, and C5a-mediated murine neutrophil migration by alpha-melanocyte-stimulating hormone.
This study was designed to examine the effects of i.p.-injected alpha-melanocyte stimulating hormone (MSH) on murine neutrophil migration into subcutaneously implanted sponges in response to IL-1-alpha, TNF-alpha, and C5a. The results show that as little as 0.1 ml of 5 x 10(-7) M MSH injected i.p. significantly blocked the accumulation of neutrophils in sponges in response to IL-1. This action of MSH was dose dependent, reversible, and was maximally effective if MSH was given at the same time as the injection of IL-1. This effect of MSH was not restricted to IL-1-induced neutrophil emigration, because MSH also antagonized the accumulation of neutrophils in response to both TNF and C5a. The proopiomelanocortin-derived peptide ACTH which contains the MSH sequence also significantly reduced neutrophil accumulation in response to IL-1, although less effectively than MSH. Similar studies with beta-endorphin showed that it had no effect on neutrophil accumulation in this system. The direct injection of MSH, beta-endorphin and ACTH into sponges or i.p. did not stimulate a neutrophil emigration and eliminated the possibility that MSH or ACTH suppressed the neutrophil influx in response to IL-1, TNF, or C5a by competing for circulating neutrophils. The action of MSH on IL-1, TNF, and C5a-induced neutrophil emigration suggests that this peptide may be an important regulator of the inflammatory response.
Mason
M J
MJ
Department of Pathology, School of Medicine, University of New Mexico, Albuquerque 87131.
Van Epps
D
D
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D003182:Complement C5; D015936:Complement C5a; D005781:Gelatin Sponge, Absorbable; D007274:Injections, Intraperitoneal; D007375:Interleukin-1; D051379:Mice; D008809:Mice, Inbred C3H; D009504:Neutrophils / Q000502:physiology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha; D000521:alpha-MSH / Q000008:administration & dosage*; D001615:beta-Endorphin / Q000494:pharmacology
D003182:Complement C5; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D000521:alpha-MSH; D001615:beta-Endorphin; D015936:Complement C5a; D000324:Adrenocorticotropic Hormone