Toxic effects of cell-free hemoglobin on the microvascular endothelium: implications for pulmonary and nonpulmonary organ dysfunction.

Levels of circulating cell-free hemoglobin are elevated during hemolytic and inflammatory diseases and contribute to organ dysfunction and severity of illness. Though several studies have investigated the contribution of hemoglobin to tissue injury, the precise signaling mechanisms of hemoglobin-mediated endothelial dysfunction in the lung and other organs are not yet completely understood. The purpose of this review is to highlight the knowledge gained thus far and the need for further investigation regarding hemoglobin-mediated endothelial inflammation and injury to develop novel therapeutic strategies targeting the damaging effects of cell-free hemoglobin.