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| http://purl.uniprot.org/citations/21746860 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/21746860 | http://purl.org/dc/terms/identifier | "doi:10.1128/iai.05043-11"xsd:string |
| http://purl.uniprot.org/citations/21746860 | http://purl.uniprot.org/core/author | "Hong H."xsd:string |
| http://purl.uniprot.org/citations/21746860 | http://purl.uniprot.org/core/author | "Johnson J.L."xsd:string |
| http://purl.uniprot.org/citations/21746860 | http://purl.uniprot.org/core/author | "Catz S.D."xsd:string |
| http://purl.uniprot.org/citations/21746860 | http://purl.uniprot.org/core/author | "Monfregola J."xsd:string |
| http://purl.uniprot.org/citations/21746860 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21746860 | http://purl.uniprot.org/core/name | "Infect Immun"xsd:string |
| http://purl.uniprot.org/citations/21746860 | http://purl.uniprot.org/core/pages | "3607-3618"xsd:string |
| http://purl.uniprot.org/citations/21746860 | http://purl.uniprot.org/core/title | "Increased survival and reduced neutrophil infiltration of the liver in Rab27a- but not Munc13-4-deficient mice in lipopolysaccharide-induced systemic inflammation."xsd:string |
| http://purl.uniprot.org/citations/21746860 | http://purl.uniprot.org/core/volume | "79"xsd:string |
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