Polymerized hemoglobin induces heme oxygenase-1 protein expression and inhibits intercellular adhesion molecule-1 protein expression in human lung microvascular endothelial cells

BACKGROUND: Our clinical trials using a polymerized hemoglobin solution (PolyHb) as a red cell substitute in severely injured patients suggested that this hemoglobin-based oxygen carrier has a systemic antiinflammatory effect. Heme oxygenase-1 (HO-1) has recently been shown to be cytoprotective, and is known to be induced by heme moieties. We investigated the effects of this hemoglobin-based oxygen carrier on HO-1 induction and proinflammatory activation of pulmonary endothelium. STUDY DESIGN: Human lung microvascular endothelial cells were grown to confluence and preincubated with either cell media (control) or with an equal volume mixture of polymerized hemoglobin/cell media (experimental). The cell cultures were subsequently stimulated with lipopolysaccharide. HO-1 expression was detected by protein immunoblot and further quantified by ELISA; intercellular adhesion molecule-1 protein expression was measured by flow cytometry. RESULTS: Polymerized hemoglobin induced synthesis of HO-1 protein in human lung microvascular endothelial cells and, concurrently, inhibited lipopolysaccharide-induced intercellular adhesion molecule-1 protein cell surface expression. CONCLUSIONS: Polymerized hemoglobin attenuates lipopolysaccharide-stimulated expression of intercellular adhesion molecule-1 protein, which is associated with upregulation of the cytoprotective protein HO-1 in human pulmonary endothelial cells. This antiinflammatory effect offers a novel mechanism by which hemoglobin-based oxygen carrier solutions may be exploited therapeutically as resuscitative fluids.