Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary.
MTA-SE "Lendület" Inflammation Physiology Research Group of the Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.
Immunol Rev. 2016 Sep;273(1):121-39. doi: 10.1111/imr.12455.
Neutrophils play a critical role in antimicrobial host defense, but their improper activation also contributes to inflammation-induced tissue damage. Therefore, understanding neutrophil biology is important for the understanding, diagnosis, and therapy of both infectious and inflammatory diseases. Neutrophils express a large number of cell-surface receptors that sense extracellular cues and trigger various functional responses through complex intracellular signaling pathways. During the last several years, we and others have shown that tyrosine kinases play a critical role in those processes. In particular, Src-family and Syk tyrosine kinases couple Fc-receptors and adhesion receptors (integrins and selectins) to various neutrophil effector functions. This pathway shows surprising similarity to lymphocyte antigen receptor signaling and involves various other enzymes (e.g. PLCγ2), exchange factors (e.g. Vav-family members) and adapter proteins (such as ITAM-containing adapters, SLP-76, and CARD9). Those mediators trigger various antimicrobial functions and play a critical role in coordinating the inflammatory response through the release of inflammatory mediators, such as chemokines and LTB4 . Interestingly, however, tyrosine kinases have a limited direct role in the migration of neutrophils to the site of inflammation. Here, we review the role of tyrosine kinase signaling pathways in neutrophils and how those pathways contribute to neutrophil activation in health and disease.
中性粒细胞在抗菌宿主防御中发挥着关键作用，但它们的不当激活也会导致炎症引起的组织损伤。因此，了解中性粒细胞生物学对于理解、诊断和治疗感染和炎症性疾病都很重要。中性粒细胞表达大量的细胞表面受体，这些受体可以感知细胞外信号，并通过复杂的细胞内信号通路触发各种功能反应。在过去的几年中，我们和其他人已经表明，酪氨酸激酶在这些过程中起着关键作用。特别是，Src 家族和 Syk 酪氨酸激酶将 Fc 受体和黏附受体（整合素和选择素）与各种中性粒细胞效应功能偶联。该途径与淋巴细胞抗原受体信号通路具有惊人的相似性，涉及其他各种酶（如 PLCγ2）、交换因子（如 Vav 家族成员）和衔接蛋白（如含有 ITAM 的衔接蛋白、SLP-76 和 CARD9）。这些介质触发各种抗菌功能，并通过释放趋化因子和 LTB4 等炎症介质在协调炎症反应中发挥关键作用。然而，有趣的是，酪氨酸激酶在中性粒细胞向炎症部位迁移中的直接作用有限。在这里，我们综述了酪氨酸激酶信号通路在中性粒细胞中的作用，以及这些通路如何在健康和疾病中促进中性粒细胞的激活。
