PEPTIDES AS WEAPONS AGAINST MICROORGANISMS IN THE CHEMICAL DEFENSE SYSTEM OF VERTEBRATES

Abstract

The innate immunity of vertebrates to microbial invasion is arbitrated by a network of host-defense mechanisms involving both the long-lasting highly specific responses of the cell-mediated immune system and a nonspecific chemical defense system based on a series of broad-spectrum antimicrobial peptides that are analogous to those found in insects. Vertebrate antibiotic peptides secreted by nonlymphoid cells of the mucosal surfaces of the respiratory and gastrointestinal tracts as well as by the granular glands of the skin reportedly cause the lysis of numerous pathogenic microorganisms, including viruses, gram-positive and gram-negative bacteria, protozoa, yeasts, and fungi, as well as of cancer cells. Antimicrobial peptides isolated from vertebrates have three characteristic properties: They are relatively small (20-46 amino acid residues), basic (lysine- or arginine-rich), and amphipathic. Although these peptides differ widely in length and amino acid sequences, they may be grouped in four broad families based on characteristic structural features. Although the precise mechanism of action of these peptides remains to be defined, their microbicidal effect very likely results from their capacity to form channels or pores within the microbial membrane in order to permeate the cell and impair its ability to carry out anabolic processes. This secondary, chemical immune system provides vertebrates with a repertoire of small peptides that are promptly synthesized upon induction, easily stored in large amounts, and readily available for antimicrobial warfare.