Journal
CYTOKINE
Volume 31, Issue 3, Pages 169-179Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.cyto.2005.04.005
Keywords
acute lung injury; neutrophils; keratinocyte-derived chemokine; macrophage inflammatory protein-2 alpha
Funding
- NHLBI NIH HHS [R01-HL73525] Funding Source: Medline
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Neutrophil associated lung injury is identified with a variety of local and systemic priming insults. In vitro studies have shown that TNF-alpha mediated suppression of neutrophil apoptosis is due to the secretion of interleukin-8 (IL-8), a human chemokine shown to alter neutrophil chemotaxis. Our initial in vitro antibody neutralization studies with neutrophil chemotactic proteins, keratinocyte-derived chemokine (KC) and macrophage inflammatory protein-2 alpha (MIP-2 alpha), mouse IL-8 homologues, indicate that MIP-2 alpha but not KC appears to mediate TNF-alpha suppression of mouse neutrophil apoptosis. Therefore, we hypothesized that in vivo neutralization of KC or MIP-2 alpha during an initial priming insult would produce differential effects on the extent of lung injury by restoring normal neutrophil apoptotic function. To assess this, mice were hemorrhaged followed with septic challenge at 24 h. Antibody against KC or MIP-2 alpha or a nonspecific IgG was given during resuscitation immediately following hemorrhage. Anti-MIP-2 alpha treatment resulted in a significant reduction in lung tissue IL-6 and myeloperoxidase levels. Percentage of neutrophil apoptosis increased significantly in the anti-KC group. Tissue and plasma KC and MIP-2 alpha were reduced in their respective treatment groups. These data suggest that KC and MIP-2 alpha differ in their mediation of neutrophil function (apoptosis and chemotaxis) and contribution to the pathogenesis of lung injury following hemorrhage subsequent to sepsis. (c) 2005 Elsevier Ltd. All rights reserved.
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