Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/101704
Title: CD163 and IgG codefend against cytotoxic hemoglobin via autocrine and paracrine mechanisms
Authors: Subramanian, Karthik
Du, Ruijuan
Tan, Nguan Soon
Ho, Bow
Ding, Jeak Ling
Keywords: DRNTU::Science::Biological sciences
Issue Date: 2013
Source: Subramanian, K., Du, R., Tan, N. S., Ho, B., & Ding, J. L. (2013). CD163 and IgG Codefend against Cytotoxic Hemoglobin via Autocrine and Paracrine Mechanisms. The Journal of Immunology, 190(10), 5267-5278.
Series/Report no.: The journal of immunology
Abstract: Lysis of RBCs during numerous clinical settings such as severe hemolytic anemia, infection, tissue injury, or blood transfusion releases the endogenous damage-associated molecular pattern, hemoglobin (Hb), into the plasma. The redox-reactive Hb generates cytotoxic reactive oxygen species, disrupting the redox balance and impairing the immune-responsive blood cells. Therefore, it is crucial to understand how the immune system defends against the cytotoxic Hb. We identified a shortcut “capture and quench” mechanism of detoxification of Hb by the monocyte scavenger receptor CD163, independent of the well-known dominant antioxidant, haptoglobin. Our findings support a highly efficient two-pass mechanism of detoxification and clearance of Hb: 1) a direct suppression of Hb-pseudoperoxidase activity by CD163, involving an autocrine loop of CD163 shedding, sequestration of Hb, recycling, and homeostasis of CD163 in human monocytes and 2) paracrine transactivation of endothelial cells by the shedded soluble CD163 (sCD163), which further detoxifies and clears residual Hb. We showed that sCD163 and IgG interact with free Hb in the plasma and subsequently the sCD163-Hb-IgG complex is endocytosed into monocytes via FcγR. The endocytosed sCD163 is recycled to restore the homeostasis of CD163 on the monocyte membrane in an autocrine cycle, whereas the internalized Hb is catabolized. Using ex vivo coculture experiments, we demonstrated that the monocyte-derived sCD163 and IgG shuttle residual plasma Hb into the proximal endothelial cells. These findings suggest that CD163 and IgG collaborate to engage monocytes and endothelial cells in a two-pass detoxification mechanism to mount a systemic defense against Hb-induced oxidative stress.
URI: https://hdl.handle.net/10356/101704
http://hdl.handle.net/10220/19771
ISSN: 0022-1767
DOI: 10.4049/jimmunol.1202648
Rights: © 2013 The American Association of Immunologists, Inc.
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SBS Journal Articles

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