Microanatomic Distribution of Myeloid Heme Oxygenase-1 Protects against Free Radical-Mediated Immunopathology in Human Tuberculosis.

Autor:	Chinta KC; Department of Microbiology, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA., Rahman MA; Africa Health Research Institute, Durban 4001, South Africa., Saini V; Department of Microbiology, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA., Glasgow JN; Department of Microbiology, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA., Reddy VP; Department of Microbiology, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA., Lever JM; Nephrology Research and Training Center, Division of Nephrology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA., Nhamoyebonde S; Africa Health Research Institute, Durban 4001, South Africa., Leslie A; Africa Health Research Institute, Durban 4001, South Africa., Wells RM; Department of Microbiology, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA., Traylor A; Nephrology Research and Training Center, Division of Nephrology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA., Madansein R; Inkosi Albert Luthuli Central Hospital, Durban 4041, South Africa., Siegal GP; Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA., Antony VB; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA., Deshane J; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA., Wells G; Africa Health Research Institute, Durban 4001, South Africa., Nargan K; Africa Health Research Institute, Durban 4001, South Africa., George JF; Division of Cardiothoracic Surgery, Department of Surgery, The University of Alabama at Birmingham, Birmingham, AL 35294, USA., Ramdial PK; Department of Anatomical Pathology, NHLS, Inkosi Albert Luthuli Central Hospital, University of KwaZulu-Natal, Durban 4091, South Africa., Agarwal A; Nephrology Research and Training Center, Division of Nephrology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Department of Veterans Affairs, Birmingham, AL 35294, USA., Steyn AJC; Department of Microbiology, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Africa Health Research Institute, Durban 4001, South Africa; UAB Center for AIDS Research, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Center for Free Radical Biology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address: asteyn@uab.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2018 Nov 13; Vol. 25 (7), pp. 1938-1952.e5.
DOI:	10.1016/j.celrep.2018.10.073
Abstrakt:	Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that controls inflammatory responses and redox homeostasis; however, its role during pulmonary tuberculosis (TB) remains unclear. Using freshly resected human TB lung tissue, we examined the role of HO-1 within the cellular and pathological spectrum of TB. Flow cytometry and histopathological analysis of human TB lung tissues showed that HO-1 is expressed primarily in myeloid cells and that HO-1 levels in these cells were directly proportional to cytoprotection. HO-1 mitigates TB pathophysiology by diminishing myeloid cell-mediated oxidative damage caused by reactive oxygen and/or nitrogen intermediates, which control granulocytic karyorrhexis to generate a zonal HO-1 response. Using whole-body or myeloid-specific HO-1-deficient mice, we demonstrate that HO-1 is required to control myeloid cell infiltration and inflammation to protect against TB progression. Overall, this study reveals that zonation of HO-1 in myeloid cells modulates free-radical-mediated stress, which regulates human TB immunopathology. (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu