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      Deciphering the Role of Heme Oxygenase-1 (HO-1) Expressing Macrophages in Renal Ischemia-Reperfusion Injury

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          Abstract

          Ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI), which contributes to the development of chronic kidney disease (CKD). Renal IRI combines major events, including a strong inflammatory immune response leading to extensive cell injuries, necrosis and late interstitial fibrosis. Macrophages act as key players in IRI-induced AKI by polarizing into proinflammatory M1 and anti-inflammatory M2 phenotypes. Compelling evidence exists that the stress-responsive enzyme, heme oxygenase-1 (HO-1), mediates protection against renal IRI and modulates macrophage polarization by enhancing a M2 subset. Hereafter, we review the dual effect of macrophages in the pathogenesis of IRI-induced AKI and discuss the critical role of HO-1 expressing macrophages.

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          Macrophage plasticity and polarization: in vivo veritas.

          Antonio Sica, Alberto Mantovani (2012)
          Diversity and plasticity are hallmarks of cells of the monocyte-macrophage lineage. In response to IFNs, Toll-like receptor engagement, or IL-4/IL-13 signaling, macrophages undergo M1 (classical) or M2 (alternative) activation, which represent extremes of a continuum in a universe of activation states. Progress has now been made in defining the signaling pathways, transcriptional networks, and epigenetic mechanisms underlying M1-M2 or M2-like polarized activation. Functional skewing of mononuclear phagocytes occurs in vivo under physiological conditions (e.g., ontogenesis and pregnancy) and in pathology (allergic and chronic inflammation, tissue repair, infection, and cancer). However, in selected preclinical and clinical conditions, coexistence of cells in different activation states and unique or mixed phenotypes have been observed, a reflection of dynamic changes and complex tissue-derived signals. The identification of mechanisms and molecules associated with macrophage plasticity and polarized activation provides a basis for macrophage-centered diagnostic and therapeutic strategies.
          Article 0 comments Cited 1104 times – based on 0 reviews     Review now
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            Protective and pathogenic functions of macrophage subsets.

            Peter Murray, Thomas Wynn (2011)
            Macrophages are strategically located throughout the body tissues, where they ingest and process foreign materials, dead cells and debris and recruit additional macrophages in response to inflammatory signals. They are highly heterogeneous cells that can rapidly change their function in response to local microenvironmental signals. In this Review, we discuss the four stages of orderly inflammation mediated by macrophages: recruitment to tissues; differentiation and activation in situ; conversion to suppressive cells; and restoration of tissue homeostasis. We also discuss the protective and pathogenic functions of the various macrophage subsets in antimicrobial defence, antitumour immune responses, metabolism and obesity, allergy and asthma, tumorigenesis, autoimmunity, atherosclerosis, fibrosis and wound healing. Finally, we briefly discuss the characterization of macrophage heterogeneity in humans.
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              Ischemia and reperfusion--from mechanism to translation.

              Holger Eltzschig, Tobias Eckle (2011)
              Ischemia and reperfusion-elicited tissue injury contributes to morbidity and mortality in a wide range of pathologies, including myocardial infarction, ischemic stroke, acute kidney injury, trauma, circulatory arrest, sickle cell disease and sleep apnea. Ischemia-reperfusion injury is also a major challenge during organ transplantation and cardiothoracic, vascular and general surgery. An imbalance in metabolic supply and demand within the ischemic organ results in profound tissue hypoxia and microvascular dysfunction. Subsequent reperfusion further enhances the activation of innate and adaptive immune responses and cell death programs. Recent advances in understanding the molecular and immunological consequences of ischemia and reperfusion may lead to innovative therapeutic strategies for treating patients with ischemia and reperfusion-associated tissue inflammation and organ dysfunction.
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                Author and article information

                Contributors
                Alexei Gratchev: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Biomedicines
                Journal ID (iso-abbrev): Biomedicines
                Journal ID (publisher-id): biomedicines
                Title: Biomedicines
                Publisher: MDPI
                ISSN (Electronic): 2227-9059
                Publication date (Electronic): 16 March 2021
                Publication date Collection: March 2021
                Volume: 9
                Issue: 3
                Electronic Location Identifier: 306
                Affiliations
                [1 ]Department of Urology, CHU de Charleroi, Université libre de Bruxelles (ULB), 6000 Charleroi, Belgium; arnaud.doerfler@ 123456chu-charleroi.be
                [2 ]Laboratory of Experimental Medicine (ULB 222 Unit), CHU de Charleroi, Hôpital André Vésale, Université libre de Bruxelles (ULB), 6110 Montigny-le-Tilleul, Belgium; keziah.korpak@ 123456chu-charleroi.be
                [3 ]Department of Geriatric Medicine, CHU de Charleroi, Hôpital André Vésale, Université libre de Bruxelles (ULB), 6110 Montigny-le-Tilleul, Belgium
                Author notes
                Author information
                https://orcid.org/0000-0002-0957-3329
                Article
                Publisher ID: biomedicines-09-00306
                DOI: 10.3390/biomedicines9030306
                PMC ID: 8002311
                SO-VID: 5ddae9a3-7a63-4024-9afe-fa90469ad7f3
                Copyright © © 2021 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 31 December 2020
                Date accepted : 10 March 2021
                Categories
                Subject: Review

                Keywords: macrophage polarization,ho-1,renal iri,aki
                Data availability:
                Keywords: macrophage polarization, ho-1, renal iri, aki

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