McCormick Barry, Chu Julia Y, Vermeren Sonja
a MRC Centre for Inflammation Research , The University of Edinburgh , Edinburgh , United Kingdom.
Small GTPases. 2019 May;10(3):187-195. doi: 10.1080/21541248.2017.1304855. Epub 2017 Apr 17.
Neutrophils are short-lived, abundant peripheral blood leukocytes that provide a first line of defense against bacterial and fungal infections while also being a key part of the inflammatory response. Chemokines induce neutrophil recruitment to inflammatory sites, where neutrophils perform several diverse functions that are aimed at fighting infections. Neutrophil effector functions are tightly regulated processes that are governed by an array of intracellular signaling pathways and initiated by receptor-ligand binding events. Dysregulated neutrophil activation can result in excessive inflammation and host damage, as is evident in several autoimmune diseases. Rho family small GTPases and agonist-activated phosphoinositide 3-kinases (PI3Ks) represent 2 classes of key regulators of the highly specialized neutrophil. Here we review cross-talk between these important signaling intermediates in the context of neutrophil functions. We include PI3K-dependent activation of Rho family small GTPases and of their guanine nucleotide exchange factors and GTPase activating proteins, as well as Rho GTPase-dependent regulation of PI3K.
中性粒细胞是寿命较短、数量丰富的外周血白细胞，它们是抵御细菌和真菌感染的第一道防线，同时也是炎症反应的关键组成部分。趋化因子诱导中性粒细胞募集到炎症部位，在那里中性粒细胞执行多种旨在对抗感染的不同功能。中性粒细胞效应功能是受一系列细胞内信号通路调控的严格过程，由受体 - 配体结合事件启动。中性粒细胞活化失调可导致过度炎症和宿主损伤，这在几种自身免疫性疾病中很明显。Rho家族小GTP酶和激动剂激活的磷脂酰肌醇3激酶（PI3K）代表了高度特化的中性粒细胞的两类关键调节因子。在这里，我们在中性粒细胞功能的背景下综述这些重要信号中间体之间的相互作用。我们包括PI3K依赖性激活Rho家族小GTP酶及其鸟嘌呤核苷酸交换因子和GTP酶激活蛋白，以及Rho GTP酶对PI3K的依赖性调节。
