期刊
BLOOD
卷 118, 期 4, 页码 1087-1098出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-10-312959
关键词
-
类别
资金
- Biotechnology and Biological Sciences Research Council
- Medical Research Council [G0700740]
- David Phillips Fellowship [BB/C520712]
- BBSRC [BB/C520712/1, BBS/E/B/0000F106] Funding Source: UKRI
- MRC [G0700740] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BBS/E/B/0000C219, BBS/E/B/0000F106, BBS/E/B/00001219, BB/C520712/1] Funding Source: researchfish
- Medical Research Council [G0700740] Funding Source: researchfish
Neutrophils form a vital part of the innate immune response, but at the same time their inappropriate activation contributes to autoimmune diseases. Many molecular components are involved in fine-tuning neutrophil function. We report here the first characterization of the role of ARAP3, a PI3K and Rap-regulated GTPase-activating protein for RhoA and Arf6 in murine neutrophils. We show that neutrophils lacking ARAP3 are preactivated in vitro and in vivo, exhibiting increased beta 2 integrin affinity and avidity. ARAP3-deficient neutrophils are hyperresponsive in several adhesion-dependent situations in vitro, including the formation of reactive oxygen species, adhesion, spreading, and granule release. ARAP3-deficient cells adhere more firmly under flow conditions in vitro and to the vessel wall in vivo. Finally, loss of ARAP3 interferes with integrin-dependent neutrophil chemotaxis. The results of the present study suggest an important function of ARAP3 downstream of Rap. By modulating beta 2 integrin activity, ARAP3 guards neutrophils in their quiescent state unless activated. (Blood. 2011; 118(4):1087-1098)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据