α-Melanocyte Stimulating Hormone Inhibits Human Epidermal Cell and Polymorphonuclear Leukocyte Chemotaxis

Abstract

Evidence is accumulating that the neuropeptide α-melanocyte stimulating hormone (a­MSH) is capable of antagonizing immune/inflammatory reactions, particularly those orchestrated by interleukin-1 (IL-1) and also by other proinflammatory principles. In order to get further insights into this activity of α-MSH, we investigated the effect of the neuropeptide on the chemotactic/chemokinetic responsiveness of freshly separated human epidermal cells (EC) and polymorphonuclear leukocytes (PMN’s) in the in vitro Boyden chamber assay. IL-1α, LTB₄, PAF, FINAP (fibroblast-derived neutrophil activating factor) and activated complement components were used as chemotactic/chemokinetic stimuli. Besides the already documented effect of IL-lα (Immunol. Letters, 22; 123), LTB₄, PAF and FINAP also exhibited potent epidermal cell chemotactic activity. α-MSH brought about a significant inhibition of the enhanced directed or random motility of both human EC and PMN’s, irrespective of the stimulus used. The optimum concentration of a-MSH for chemotaxis/chemokinesis inhibition was in the range of 10^-7 M. The neuropeptide did not compete with the chemoattractants. A competitive inhibition/chemotactic deactivation is, therefore, not a likely mechanism underlying the action of the neuropeptide. To our knowledge, this is the first documentation of this novel aspect of a broad spectrum antiinflammatory activity of the neuropeptide on freshly obtained human cells, i.e. EC and PMN’s