ANTILEUKOPROTEASE IN HUMAN SKIN - AN ANTIBIOTIC PEPTIDE CONSTITUTIVELY PRODUCED BY KERATINOCYTES

Antileukoprotease (ALP), also known as mucous protease inhibitor or se cretory leukoprotease inhibitor, resembles one of the major antiprotea ses present in human body fluids. It is capable of preventing proteoly tic degradation of extracellular matrix proteins by neutrophil-derived serine proteases. ALP was isolated from human callus and detected in supernatants of cultured human primary keratinocytes. ALP mRNA was con stitutively expressed in keratinocytes and the expression was not sign ificantly affected by TNF alpha or Interferon gamma stimulation. In mi crobicidal assays recombinant ALP exhibited antimicrobial activity aga inst several human skin associated microorganisms like P. aeruginosa, S. aureus, S. epidermidis, and C. albicans, indicating that ALP may ac tively participate in mechanisms allowing homeostasis of bacterial and yeast colonization on human skin. Thus, ALP represents a major solubl e serine protease inhibitor and antimicrobial agent expressed in human skin and seems to contribute to the high resistance of the epidermis against proteolysis and infections. (C) 1998 Academic Press.