Rab27在中性粒细胞趋化作用和肺募集过程中的作用。

A role for Rab27 in neutrophil chemotaxis and lung recruitment.

作者信息

Singh Rajesh K, Furze Rebecca C, Birrell Mark A, Rankin Sara M, Hume Alistair N, Seabra Miguel C

出版信息

BMC Cell Biol. 2014 Oct 31;15:39. doi: 10.1186/s12860-014-0039-z.

BACKGROUND

Neutrophils are a critical part of the innate immune system. Their ability to migrate into infected or injured tissues precedes their role in microbial killing and clearance. We have previously shown that Rab27a can promote neutrophil migration by facilitating uropod release through protease secretion from primary granule exocytosis at the cell rear. Rab27b has been implicated in primary granule exocytosis but its role in neutrophil migration has not been investigated.

RESULTS

Here we found Rab27b to be expressed in bone marrow derived neutrophils and Rab27b knockout (Rab27b KO) along with Rab27a/b double knockout (Rab27DKO) neutrophils exhibited impaired transwell migration in vitro in response to chemokines MIP-2 and LTB4. Interestingly, no additional defect in migration was observed in Rab27DKO neutrophils compared with Rab27b KO neutrophils. In vivo, Rab27DKO mice displayed severe impairment in neutrophil recruitment to the lungs in a MIP-2 dependent model but not in an LPS dependent model.

CONCLUSIONS

These data taken together implicate Rab27b in the regulation of neutrophil chemotaxis, likely through the regulation of primary granule exocytosis.

背景

中性粒细胞是固有免疫系统的关键组成部分。它们迁移至感染或损伤组织的能力先于其在微生物杀伤和清除中的作用。我们之前已经表明，Rab27a可通过促进细胞尾部初级颗粒胞吐产生的蛋白酶分泌来促进足突释放，从而促进中性粒细胞迁移。Rab27b与初级颗粒胞吐有关，但其在中性粒细胞迁移中的作用尚未得到研究。

结果

在此我们发现Rab27b在骨髓来源的中性粒细胞中表达，并且Rab27b基因敲除（Rab27b KO）以及Rab27a/b双基因敲除（Rab27DKO）的中性粒细胞在体外对趋化因子MIP-2和LTB4的反应中，其穿膜迁移受损。有趣的是，与Rab27b KO中性粒细胞相比，Rab27DKO中性粒细胞在迁移方面未观察到额外缺陷。在体内，Rab27DKO小鼠在依赖MIP-2的模型中，中性粒细胞向肺部的募集显示出严重受损，但在依赖脂多糖的模型中则未受损。