Abstract
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.
Highlights
Neutrophils are a critical part of the innate immune system
We used a transwell migration assay to examine the in vitro chemotaxis of Rab27b KO bone marrow derived neutrophil (BMDN). Both Rab27b KO and Rab27DKO neutrophils displayed significantly impaired transwell chemotaxis compared with wild-type neutrophils using macrophage inflammatory protein 2 (MIP-2) (Figure 1B) and leukotriene B4 (LTB4) (Figure 1C) to stimulate chemotaxis
A comparison of Rab27a deficient, Rab27b KO and Rab27DKO neutrophil chemotaxis in response to MIP-2 suggested that there is a similar level of impairment in all 3 mutant neutrophil types using three different concentrations of MIP-2 (Figure 1D)
Summary
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. Neutrophils make up part of the innate immune system and provide the first line of defense against pathogens [1] They can kill microbes in several different ways, often directly ingesting microbes or releasing microbicidal products or reactive oxygen species in their vicinity [2]. To exact these effector functions, neutrophils must first have the ability to migrate towards microbes. The ability of neutrophils to migrate effectively is critical to bring them into proximity to microbes to allow
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