title: A role for Rab27 in neutrophil chemotaxis and lung recruitment.
abstract: 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.
authors.forename: Rajesh K
authors.initials: RK
authors.lastname: Singh
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Furze
authors.forename: Mark A
authors.initials: MA
authors.lastname: Birrell
authors.forename: Sara M
authors.initials: SM
authors.lastname: Rankin
authors.forename: Alistair N
authors.initials: AN
authors.lastname: Hume
authors.forename: Miguel C
authors.initials: MC
authors.lastname: Seabra
mesh_terms: D000818:Animals; D002465:Cell Movement; D054426:Chemokine CXCL2 / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000032:analysis; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000276:immunology*; D000075745:rab27 GTP-Binding Proteins
chemical_list: D054426:Chemokine CXCL2; D008070:Lipopolysaccharides; D023063:Receptors, Interleukin-8B; D000075745:rab27 GTP-Binding Proteins; C512958:Rab27b protein, mouse; C512962:Rab27a protein, mouse; D020691:rab GTP-Binding Proteins