Human neutrophils coordinate chemotaxis by differential activation of Rac1 and Rac2.
Human neutrophils coordinate chemotaxis by differential activation of Rac1 and Rac2.
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DOI：
10.4049/jimmunol.0900849
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发表时间：
2009-08-15
期刊：
影响因子：
--
通讯作者：
Bokoch GM
中科院分区：
文献类型：
--
作者：
Zhang H;Sun C;Glogauer M;Bokoch GM
Rac1 and Rac2, members of the small Rho GTPase family, play essential roles in coordinating directional migration and superoxide production during neutrophil responses to chemoattractants. While earlier studies in Rac1 and Rac2 knockout mice have demonstrated unique roles for each Rac isoform in chemotaxis and NADPH oxidase activation, it is still unclear how human neutrophils utilize Rac1 and Rac2 to achieve their immunological responses to foreign agent stimulation. In the current study, we used TAT-dominant negative Rac1-T17N and Rac2-T17N fusion proteins to acutely alter the activity of Rac1 and Rac2 individually in human neutrophils. We demonstrate distinct activation kinetics and different roles for Rac1 and Rac2 in response to low versus high concentrations of fMLP. These observations were verified using neutrophils from mice in which Rac1 or Rac2 was genetically absent. Based on these results, we propose a model to explain how human neutrophils kill invading microbes while limiting oxidative damage to the adjacent surrounding healthy tissue through the differential activation of Rac1 and Rac2 in response to different concentrations of chemoattractant.
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