Local anesthetic interactions with host defense mechanisms of human neutrophils - effects on signaling of chemotaxis, oxidative burst and phagocytosis.

点击翻译按钮获取中文摘要

The systemic application of local anesthetics (LA) intra- and postoperatively results in an amelioration of several inflammation-mediated disorders. E.g. the duration of postoperative ileus been shown to be drastically reduced by intravenous lidocaine administration in patients with major abdominal surgery.In vitro, we have probed mechanisms of action on immunocompetent cells. One target identified is the Gq protein, which is inhibited in a time-dependent and reversible manner by low concentrations of local anesthetics. This inhibition of Gq protein function seems to be responsible for the ability of local anesthetics to inhibit priming of extracellular superoxide release. However, the neutrophil response to injury has many aspects, and for other key functions of the host defense we only have rather superficial information as to their local anesthetic sensitivity.The purpose of this project is to clarify, if LA modulate key functions of the host defense (leukocyte chemotaxis, phagocytosis and oxidative burst) by the same intracellular pathway of Gq protein inhibition as already shown for superoxide release and if the inhibtion of these leukocyte functions is also time dependent.