Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/48389
Title: CD163-MEDIATED INNATE IMMUNE RESPONSE(S) TO CELL-FREE HEMOGLOBIN
Authors: KARTHIK SUBRAMANIAN
Keywords: Hemoglobin, CD163, IgG, oxidative stress, monocytes/macrophages, intracellular infection
Issue Date: 15-Aug-2013
Source: KARTHIK SUBRAMANIAN (2013-08-15). CD163-MEDIATED INNATE IMMUNE RESPONSE(S) TO CELL-FREE HEMOGLOBIN. ScholarBank@NUS Repository.
Abstract: Hemolysis induced during infection, injury/trauma and genetic disorders releases excessive level of free hemoglobin (Hb) into the plasma. Plasma Hb is cytotoxic owing to its redox reactivity and releases damaging reactive oxygen species. Hence, rapid clearance of plasma Hb is crucial for survival. We found a novel two-pass Hb-detoxification and clearance mechanism involving the monocyte/macrophage scavenger receptor, CD163, plasma IgG and vascular endothelial cells that becomes operative under conditions of severe hemolysis when haptoglobin, the predominant Hb-sequestering plasma protein is exhausted. Our elucidation of the detoxification mechanism involving endocytosis of Hb into monocytes, prompted us to examine the pathophysiological consequence of Hb-priming on the host cell viability and intracellular bacterial clearance during hemolytic infections. We found that opportunistic bacteria such as Staphylococcus and Salmonella exploit the host¿s Hb-scavenging mechanism and preferentially survive inside the Hb-loaded macrophages to hijack the nutrient iron, while simultaneously inhibiting host cell apoptosis for its survival.
URI: http://scholarbank.nus.edu.sg/handle/10635/48389
Appears in Collections:Ph.D Theses (Open)

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