Critical protective role for annexin 1 gene expression in the endotoxemic murine microcirculation

Critical protective role for annexin 1 gene expression in the endotoxemic murine microcirculation

Author Damazo, Amilcar Sabino Autor UNIFESP Google Scholar
Yona, Simon Google Scholar
D'Acquisto, Fulvio Google Scholar
Flower, Roderick J. Google Scholar
Oliani, Sonia M. Autor UNIFESP Google Scholar
Perretti, Mauro Google Scholar
Institution Queen Mary Sch Med & Dent
Universidade Federal de São Paulo (UNIFESP)
Univ Estado São Paulo
Abstract The inflammatory response is a protective process of the body to counteract xenobiotic penetration and injury, although in disease this response can become deregulated. There are endogenous biochemical pathways that operate in the host to keep inflammation under control. Here we demonstrate that the counter-regulator annexin 1 (AnxA1) is critical for controlling experimental endotoxemia. Lipopolysaccharide (LPS) markedly activated the AnxA1 gene in epithelial cells, neutrophils, and peritoneal, mesenteric, and alveolar macrophages cell types known to function in experimental endotoxemia. Administration of LPS to AnxA1-deficient mice produced a toxic response characterized by organ injury and lethality within 48 hours, a phenotype rescued by exogenous application of low doses of the protein. in the absence of AnxA1, LPS generated a deregulated cellular and cytokine response with a marked degree of leukocyte adhesion in the microcirculation. Analysis of LPS receptor expression in AnxA1-null macrophages indicated an aberrant expression of Toll-like receptor 4. in conclusion, this study has detailed cellular and biochemical alterations associated with AnxA1 gene deletion and highlighted the impact of this protective circuit for the correct functioning of the homeostatic response to sublethal doses of LPS.
Language English
Date 2005-06-01
Published in American Journal of Pathology. Bethesda: Amer Soc Investigative Pathology, Inc, v. 166, n. 6, p. 1607-1617, 2005.
ISSN 0002-9440 (Sherpa/Romeo, impact factor)
Publisher Amer Soc Investigative Pathology, Inc
Extent 1607-1617
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000229387100004

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