Signal Transduction Pathways Regulating Neutrophil Effector Functions

摘要

Human polymorphic granulocytes can be divided into three distinct types: neutrophils, eosinophils and basophils. While all three play a role in allergic inflammation, only neutrophils and eosinophils are phagocytic cells which play a critical role in host defence against microbial infection. At the site of infection the granulocyte participates in the inflammatory reaction by killing of microorganisms and production of inflammatory mediators. An unfortunate consequence of activation is the ability to cause tissue damage during acute inflammation and thus the activity of granulocytes must be tightly controlled. The bone marrow generates approximately 60-400x10~7 neutrophils per day and once released into the peripheral blood they have a half-life of roughly 6-9 hours. These cells express a wide variety of cell surface receptors regulating both activation and effector functions. Utilising pharmacological inhibitors, the roles of different signalling pathways in the regulation of neutrophil function have been investigated. This review summarises our current knowledge on the roles of Mitogen Activated Protein Kinases, phosphatidylinositol 3-kinases and [Ca~(2+)]; in regulating neutrophil effector functions and survival.