Antimicrobial effects of a-MSH peptides

Abstract: The presence of the ancient anti-inflammatory peptide a-melanocyte-stimulating hormone [a-MSH (1–13), SYSMEHFRWGKPV] in barrier organs such as gut and skin suggests a role in the nonspecific (innate) host defense. a-MSH and and its carboxy-terminal tripeptide (11–13, KPV) were determined to have antimicrobial influences against two major and representative pathogens: Staphylococcus aureus and Candida albicans. a-MSH peptides significantly inhibited S. aureus colony formation and reversed the enhancing effect of urokinase on colony formation. Antimicrobial effects occurred over a broad range of concentra-tions including the physiological (picomolar) range. Small concentrations of a-MSH peptides likewise reduced viability and germ tube formation of the yeast C. albicans. Antimicrobial influences of a-MSH peptides could be mediated by their capac-ity to increase cellular cAMP. Indeed, this messen-ger was significantly augmented in peptide-treated yeast and the potent adenylyl cyclase inhibitor dideoxyadenosine (ddAdo) partly reversed the kill-ing activity of a-MSH peptides. Reduced killing of pathogens is a detrimental consequence of therapy with anti-inflammatory drugs. Because a-MSH has potent anti-inflammatory effects we determined influences of a-MSH on C. albicans and S. aureus killing by human neutrophils. a-MSH peptides did not reduce killing but rather enhanced it, likely as a consequence of the direct antimicrobial activity. a-MSH peptides that combine antipyretic, anti-inflammatory, and antimicrobial effects could be useful in treatment of disorders in which infection and inflammation coexist. J. Leukoc. Biol. 67