Neutrophil antibacterial peptides, multifunctional effector molecules in the mammalian immune system

The bactericidal machinery of mammalian neutrophils is built up of many com ponents with different chemical properties, involving proteins, peptides an d oxygen-dependent radicals. All these components work in synergy, leading to destruction and elimination of ingested microbes. During the eighties, i t gradually became clear, that cationic peptides are a part of the oxygen-i ndependent bactericidal effecters in phagocytic cells. In mammals, these an timicrobial peptides are represented by two families, the defensins and the cathelicidins. These potent broad spectra peptides are included as immedia te effector molecules in innate immunity. The detailed killing mechanism fo r these effectors is partly known, but nearly all of them have membrane aff inity, and permeate bacterial membranes, resulting in lysis of the bacteria . This peptide-membrane interaction includes also eukaryotic membranes, tha t implicates cytotoxic effects on host cells. Studies in vitro have establi shed that the microenvironment is critical for their activities. In connect ion to cystic fibrosis, the effects of microenvironment changes are apparen t, causing inactivation of peptide defences and leading to repeated serious bacterial infections. Thus, the importance of the microenvironment is also supported in vivo. Additional functions of these peptides such as chemotac tic, mitogenic and stimulatory in the wound healing process suggest further important roles for these peptides. (C) 1999 Elsevier Science B.V. All rig hts reserved.