Direct and alternative antimicrobial mechanisms of neutrophil-derived granule proteins

Abstract

Polymorphonuclear leukocytes (PMN) contribute to bacterial clearance by uptake and intracellular killing of microbes. However, antimicrobial polypeptides are released extracellularly where they are enweaved in a chromatin web that traps and eliminates bacteria. In addition, PMN-derived antimicrobial polypeptides direct monocytes and macrophages to the site of infection and activate their antimicrobial armor. Increased expression of Fcgamma receptors as well as opsonization of bacteria by PMN granule proteins support bacterial uptake by macrophages. PMN granule proteins also increase intracellular reactive oxygen species formation in macrophages. Finally, apoptotic PMN transfer parts of their antimicrobial peptides to macrophages, hence increasing killing of intracellular bacteria. Understanding mechanisms by which PMN granule proteins stimulate antimicrobial mechanisms in macrophages may open novel strategies in fighting bacterial infections.