The 5-Phosphatase SHIP2 Promotes Neutrophil Chemotaxis and Recruitment.
The 5-Phosphatase SHIP2 Promotes Neutrophil Chemotaxis and Recruitment.
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DOI：
10.3389/fimmu.2021.671756
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发表时间：
2021
影响因子：
7.3
通讯作者：
Vermeren S
中科院分区：
文献类型：
--
作者：
Michael M;McCormick B;Anderson KE;Karmakar U;Vermeren M;Schurmans S;Amour A;Vermeren S
中性粒细胞是人类最丰富的循环白细胞，在宿主防御和炎症反应中起关键作用。激动剂激活的磷酸肌醇3-激酶（PI 3 Ks）是中性粒细胞生物学的许多方面的重要调节剂。PIP 3通过几种5'磷酸酶（包括SHIP家族磷酸酶）进行去磷酸化，所述磷酸酶将PI 3 K产物和脂质第二信使磷脂酰肌醇3，4，5-三磷酸（PIP 3）转化为PI（3，4）P2，其本身是脂质第二信使。除了白细胞限制性SHIP 1之外，中性粒细胞表达普遍存在的SHIP 2。本研究分析了携带无催化活性SHIP 2的小鼠和分离的嗜中性粒细胞，鉴定了体外嗜中性粒细胞趋化性和方向性以及体内嗜中性粒细胞向无菌炎症部位募集的重要调节功能，其中没有分析的任何其他嗜中性粒细胞功能的主要缺陷，包括吞噬作用和活性氧物质的形成。从机制上讲，这是通过对全局3-磷酸化磷酸肌醇种类的微妙影响来解释的。这项工作确定了一个非冗余的作用，迄今为止被忽视的SHIP 2在调节中性粒细胞，特别是中性粒细胞趋化性/贩运。它完成了对中性粒细胞中PI 3 K信号传导复杂性的更广泛理解，以及单个激酶和磷酸酶在其中所起的作用。
Neutrophils, the most abundant circulating leukocytes in humans have key roles in host defense and in the inflammatory response. Agonist-activated phosphoinositide 3-kinases (PI3Ks) are important regulators of many facets of neutrophil biology. PIP3 is subject to dephosphorylation by several 5’ phosphatases, including SHIP family phosphatases, which convert the PI3K product and lipid second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3) into PI(3,4)P2, a lipid second messenger in its own right. In addition to the leukocyte restricted SHIP1, neutrophils express the ubiquitous SHIP2. This study analyzed mice and isolated neutrophils carrying a catalytically inactive SHIP2, identifying an important regulatory function in neutrophil chemotaxis and directionality in vitro and in neutrophil recruitment to sites of sterile inflammation in vivo, in the absence of major defects of any other neutrophil functions analyzed, including, phagocytosis and the formation of reactive oxygen species. Mechanistically, this is explained by a subtle effect on global 3-phosphorylated phosphoinositide species. This work identifies a non-redundant role for the hitherto overlooked SHIP2 in the regulation of neutrophils, and specifically, neutrophil chemotaxis/trafficking. It completes an emerging wider understanding of the complexity of PI3K signaling in the neutrophil, and the roles played by individual kinases and phosphatases within.
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影响因子：
9.8
作者：
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通讯作者：
Boucrot E