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      Macrophages in solid organ transplantation

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          Abstract

          Macrophages are highly plastic hematopoietic cells with diversified functions related to their anatomic location and differentiation states. A number of recent studies have examined the role of macrophages in solid organ transplantation. These studies show that macrophages can induce allograft injury but, conversely, can also promote tissue repair in ischemia-reperfusion injury and acute rejection. Therapeutic strategies that target macrophages to improve outcomes in solid organ transplant recipients are being examined in preclinical and clinical models. In this review, we discuss the role of macrophages in different types of injury and rejection, with a focus on macrophage-mediated tissue injury, specifically vascular injury, repair and remodeling. We also discuss emerging macrophage-centered therapeutic opportunities in solid organ transplantation.

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          Local macrophage proliferation, rather than recruitment from the blood, is a signature of TH2 inflammation.

          A defining feature of inflammation is the accumulation of innate immune cells in the tissue that are thought to be recruited from the blood. We reveal that a distinct process exists in which tissue macrophages undergo rapid in situ proliferation in order to increase population density. This inflammatory mechanism occurred during T helper 2 (T(H)2)-related pathologies under the control of the archetypal T(H)2 cytokine interleukin-4 (IL-4) and was a fundamental component of T(H)2 inflammation because exogenous IL-4 was sufficient to drive accumulation of tissue macrophages through self-renewal. Thus, expansion of innate cells necessary for pathogen control or wound repair can occur without recruitment of potentially tissue-destructive inflammatory cells.
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            Macrophage regulation of tumor responses to anticancer therapies.

            Tumor-associated macrophages (TAMs) promote key processes in tumor progression, like angiogenesis, immunosuppression, invasion, and metastasis. Increasing studies have also shown that TAMs can either enhance or antagonize the antitumor efficacy of cytotoxic chemotherapy, cancer-cell targeting antibodies, and immunotherapeutic agents--depending on the type of treatment and tumor model. TAMs also drive reparative mechanisms in tumors after radiotherapy or treatment with vascular-targeting agents. Here, we discuss the biological significance and clinical implications of these findings, with an emphasis on novel approaches that effectively target TAMs to increase the efficacy of such therapies. Copyright © 2013 Elsevier Inc. All rights reserved.
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              Cell death.

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                Author and article information

                Contributors
                Journal
                Vasc Cell
                Vascular Cell
                BioMed Central
                2045-824X
                2014
                11 March 2014
                : 6
                : 5
                Affiliations
                [1 ]Department of Medicine, VA Palo Alto Health Care System/Division of Pulmonary/Critical Care, Stanford University School of Medicine, Stanford, CA 94304, USA
                [2 ]VA Palo Alto Health Care System, Bldg 101, A4-151, 3801 Miranda Ave, Palo Alto, CA 94304, USA
                [3 ]VA Palo Alto Health Care System, Med111P, 3801 Miranda Ave, Palo Alto, CA 94304, USA
                Article
                2045-824X-6-5
                10.1186/2045-824X-6-5
                3975229
                24612731
                60f08c20-90d4-48e5-b85e-59034c2dd459
                Copyright © 2014 Jiang et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 28 November 2013
                : 25 February 2014
                Categories
                Review

                Cell biology
                macrophage,transplantation,ischemia reperfusion injury,acute rejection,graft vascular disease

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