Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense
Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense
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DOI：
10.1016/s1074-7613(00)80019-9
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发表时间：
1999-02-01
期刊：
影响因子：
32.4
通讯作者：
Williams, DA
中科院分区：
文献类型：
--
作者：
Roberts, AW;Kim, C;Williams, DA
在哺乳动物中，Rho家族GTCRac 2的表达限于造血细胞，在造血细胞中它与Rac 1共表达。Rac 2缺陷小鼠被创建以确定造血细胞中两种几乎相同的Pac蛋白的生理需求，rac 2（-/-）中性粒细胞在趋化性、剪切依赖性L-选择素介导的对内皮底物Glycam-1的捕获、F-肌动蛋白生成和p38以及由化学引诱物诱导的p42/ p44 MAP激酶激活方面显示出显著缺陷。与野生型相比，rac 2（-/-）骨髓中性粒细胞的超氧化物产生显著减少，但在活化的腹膜渗出液中性粒细胞中是正常的。这些缺陷反映在体内基线嗜中性粒细胞，减少炎性腹膜渗出液的形成，并增加死亡率时，挑战烟曲霉菌。Rac 2是多种特化中性粒细胞功能的重要调节因子。
In mammals, the Rho family GTPase Rac2 is restricted in expression to hematopoietic cells, where it is coexpressed with Rac1. Rac2-deficient mice were created to define the physiological requirement for two near-identical Pac proteins in hematopoietic cells, rac2(-/-) neutrophils displayed significant defects in chemotaxis, in shear-dependent L-selectin-mediated capture on the endothelial substrate Glycam-1, and in both F-actin generation and p38 and, unexpectedly, p42/ p44 MAP kinase activation induced by chemoattractants. Superoxide production by rac2(-/-) bone marrow neutrophils was significantly reduced compared to wild type, but it was normal in activated peritoneal exudate neutrophils. These defects were reflected in vivo by baseline neutrophilia, reduced inflammatory peritoneal exudate formation, and increased mortality when challenged with Aspergillus fumigatus. Rac2 is an essential regulator of multiple specialized neutrophil functions.