Molecular events in the activation of human neutrophils for microbial killing.

Abstract

Human neutrophils provide protection from a variety of microbes; neutropenia or neutrophil dysfunction can both have serious clinical consequences. Effective microbial killing involves attachment to blood vessel walls, transmigration into tissues, chemotaxis, and phagocytosis. The molecular mechanisms by which neutrophils kill microbes have been extensively dissected. Each of the cellular processes is initiated in response to the occupancy of unique surface receptors. Receptor occupancy is translated into specific cellular activities via such signals as activation of calcium-mediated protein kinases and phosphorylation of critical proteins. After phagocytosis, the engulfed particle is subjected to killing mechanisms, which include reactive oxygen species, acid pH, and antimicrobial proteins. A thorough understanding of these molecular events may allow the modulation of neutrophil activity.