NDLI: Increased Survival and Reduced Neutrophil Infiltration of the Liver in Rab27a- but Not Munc13-4-Deficient Mice in Lipopolysaccharide-Induced Systemic Inflammation ▿

Content Provider	PubMed Central
Author	Johnson, Jennifer L. Hong, Hong Monfregola, Jlenia Catz, Sergio D.
Editor	Blanke, S. R.
Copyright Year	2011
Abstract	Genetic defects in the Rab27a or Munc13-4 gene lead to immunodeficiencies in humans, characterized by frequent viral and bacterial infections. However, the role of Rab27a and Munc13-4 in the regulation of systemic inflammation initiated by Gram-negative bacterium-derived pathogenic molecules is currently unknown. Using a model of lipopolysaccharide-induced systemic inflammation, we show that Rab27a-deficient (Rab27a ash / ash ) mice are resistant to lipopolysaccharide (LPS)-induced death, while Munc13-4-deficient (Munc13-4 jinx / jinx ) mice show only moderate protection. Rab27a ash / ash but not Munc13-4 jinx / jinx mice showed significantly decreased tumor necrosis factor alpha (TNF-α) plasma levels after LPS administration. Neutrophil sequestration in lungs from Rab27a ash / ash and Munc13-4 jinx / jinx LPS-treated mice was similar to that observed for wild-type mice. In contrast, Rab27a- but not Munc13-4-deficient mice showed decreased neutrophil infiltration in liver and failed to undergo LPS-induced neutropenia. Decreased liver infiltration in Rab27a ash / ash mice was accompanied by lower CD44 but normal CD11a and CD11b expression in neutrophils. Both Rab27a- and Munc13-4-deficient mice showed decreased azurophilic granule secretion in vivo, suggesting that impaired liver infiltration and improved survival in Rab27a ash / ash mice is not fully explained by deficient exocytosis of this granule subset. Altogether, our data indicate that Rab27a but not Munc13-4 plays an important role in neutrophil recruitment to liver and LPS-induced death during endotoxemia, thus highlighting a previously unrecognized role for Rab27a in LPS-mediated systemic inflammation.
Related Links	http://dx.doi.org/10.1128/iai.05043-11
Ending Page	3618
Page Count	12
Starting Page	3607
File Format	PDF
ISSN	00199567
e-ISSN	10985522
Journal	Infection and Immunity
Issue Number	9
Volume Number	79
Language	English
Publisher	American Society for Microbiology
Publisher Date	2011-09-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Immunology Microbiology Parasitology Infectious Diseases Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Parasitology Immunology Microbiology

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