A role for Rab27 in neutrophil chemotaxis and lung recruitment

BMC Cell Biology

Research Article

Rebecca C Furze¹  Sara M Rankin¹  Miguel C Seabra²  Alistair N Hume³  Rajesh K Singh⁴  Mark A Birrell⁵ 

[1] Leukocyte Biology, National Heart and Lung Institute, Imperial College London, London, UK;Molecular Medicine, National Heart and Lung Institute, Imperial College London, London, UK;Molecular Medicine, National Heart and Lung Institute, Imperial College London, London, UK;School of Biomedical Sciences, University of Nottingham, Nottingham, UK;Molecular Medicine, National Heart and Lung Institute, Imperial College London, London, UK;Weill Cornell Medical College, 1300 York Avenue, 10065, New York, NY, USA;Respiratory Pharmacology, National Heart and Lung Institute, Imperial College London, London, UK;

关键词: Rab27;    Neutrophil;    Chemotaxis;    Exocytosis;   

DOI  :  10.1186/s12860-014-0039-z

 received in 2014-07-16, accepted in 2014-10-16,  发布年份 2014

来源: Springer

【 摘 要 】

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

【 授权许可】

CC BY   
© Singh et al.; licensee BioMed Central Ltd. 2014