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Am J Physiol Heart Circ Physiol 2004 Oct;287(4):H1875-82

Redox active hemoglobin enhances lipopolysaccharide-induced injury to cultured bovine endothelial cells.

D'Agnillo F

D'Agnillo F, US FDA, Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Div Hematol, 29 Lincoln Dr,Bldg 29,Rm 129, Bethesda, MD 20892 USA US FDA, Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Div Hematol, Bethesda, MD 20892 USA

Abstract

The interaction of cell-free hemoglobin with lipopolysaccharide (LPS) is thought to aggravate the pathophysiology of sepsis and/or septic shock. This study examines the possible modulatory role of cell-free hemoglobin on LPS-induced apoptosis of cultured bovine aortic endothelial cells. Experiments were performed with or without fetal bovine serum, a source of LPS-binding protein and soluble CD14. In the absence of serum, LPS alone or co-incubated with purified bovine hemoglobin (BvHb), human hemoglobin (Hb) or alpha cross-linked human hemoglobin (alphaalphaHb) did not induce apoptosis. In the presence of serum, LPS induced significant apoptosis. LPS combined with BvHb, Hb or alphaalphaHb produced the same extent of apoptosis as LPS alone. To examine whether the hydrogen peroxide (H2O2)-driven redox activity of hemoglobin alters LPS-induced apoptosis, glucose oxidase was added to the system to generate a subtoxic flux of H2O2. The combined treatment of LPS, glucose oxidase and BvHb, Hb or alphaalphaHb enhanced apoptosis compared to LPS alone. These findings support a possible mechanism whereby the redox cycling of hemoglobin, and not its direct interaction with LPS, contributes to the hemoglobin-mediated enhancement of LPS-related pathophysiology.


Category: Journal Article, Peer
PubMed ID: #15205170
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29
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