Vasculotoxic and Proinflammatory Effects of Plasma Heme: Cell Signaling and Cytoprotective Responses. (24th June 2013)

• Record Type: Journal Article
• Authors: Belcher, John D.; Nath, Karl A.; Vercellotti, Gregory M.
• Other Names: Fato R. Academic Editor.; Iles K. Academic Editor.
• Is Part Of: ISRN oxidative medicine. Volume 2013(2013)
• Publication Date: 2013-06-24
• Subjects: Medicine -- Periodicals; Electronic journals; Periodicals; 610
• DOI: 10.1155/2013/831596
• Languages: English
• ISSNs: 2314-6400

Abstract

Abstract : The proinflammatory vasculotoxic effects of intravascular hemolysis are modulated by plasma hemoglobin and heme clearance via the haptoglobin/CD163 system and the hemopexin/CD91 system, respectively, and detoxification through the heme oxygenase/ferritin system. However, sudden or excessive hemolysis can overwhelm these protective systems leading to heme interacting with cells of the vasculature. Heme presents a damage-associated molecular pattern to the innate immune system. Heme is an extracellular inflammatory signaling molecule with strict binding specificity for TLR4 on monocyte/macrophages, endothelial, and other cells. The resulting TLR4 signaling cascade rapidly leads to intracellular oxidative stress and an inflammatory response. Heme also induces a cytoprotective response that includes Nrf2 responsive genes such as heme oxygenase-1, ferritin, haptoglobin, hemopexin, and other antioxidant response genes. It is the balance between the pro-inflammatory/vasculotoxic effects of plasma hemoglobin/heme and the cytoprotective responses that ultimately determines the pathophysiologic outcome in patients.