Signaling mechanisms in human neutrophils

Leukocytes possess many properties critical to their effective functioning in inflammation, including the ability to migrate to the site of inflammation and release an impressive armamentarium of toxic products such as proteolytic enzymes, reactive oxygen species, and cationic proteins, capable of killing invading pathogens. This review focuses on the transmembrane signaling events whereby factors present in an inflammatory milieu activate these leukocyte effector functions. In the past several years, many of the components of these pathways have been elucidated at the molecular level, but large gaps remain in our understanding. The discussion follows the path beginning from the exofacial side of the plasma membrane toward the cell interior: from membrane receptors, GTP-binding proteins and adapter proteins to intermediary pathways including phospholipases and protein kinases. A detailed understanding of these regulatory mechanisms will have important therapeutic implications for amelioration of inflammatory tissue injury.