4.7 Article

The GTPase-activating protein ARAP3 regulates chemotaxis and adhesion-dependent processes in neutrophils

期刊

BLOOD
卷 118, 期 4, 页码 1087-1098

出版社

AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-10-312959

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资金

  1. Biotechnology and Biological Sciences Research Council
  2. Medical Research Council [G0700740]
  3. David Phillips Fellowship [BB/C520712]
  4. BBSRC [BB/C520712/1, BBS/E/B/0000F106] Funding Source: UKRI
  5. MRC [G0700740] Funding Source: UKRI
  6. Biotechnology and Biological Sciences Research Council [BBS/E/B/0000C219, BBS/E/B/0000F106, BBS/E/B/00001219, BB/C520712/1] Funding Source: researchfish
  7. Medical Research Council [G0700740] Funding Source: researchfish

向作者/读者索取更多资源

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)

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