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      Inflammatory Manifestations of Lymphedema

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          Abstract

          Lymphedema results from lymphatic insufficiency leading to a progressive inflammatory process that ultimately manifests as discomfort, recurrent infections, and, at times, secondary malignancy. Collectively, these morbidities contribute to an overall poor quality of life. Although there have been recent advances in microsurgical interventions, a conservative palliative approach remains the mainstay of treatment for this disabling disease. The absence of a cure is due to an incomplete understanding of the pathophysiological changes that result in lymphedema. A histological hallmark of lymphedema is inflammatory cell infiltration and recent studies with animal models and clinical biopsy specimens have suggested that this response plays a key role in the pathology of the disease. The purpose of this report is to provide an overview of the ongoing research in and the current understanding of the inflammatory manifestations of lymphedema.

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          Most cited references66

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          Fibrotic disease and the T(H)1/T(H)2 paradigm.

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            Macrophages: master regulators of inflammation and fibrosis.

            Macrophages are found in close proximity with collagen-producing myofibroblasts and indisputably play a key role in fibrosis. They produce profibrotic mediators that directly activate fibroblasts, including transforming growth factor-beta1 and platelet-derived growth factor, and control extracellular matrix turnover by regulating the balance of various matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases. Macrophages also regulate fibrogenesis by secreting chemokines that recruit fibroblasts and other inflammatory cells. With their potential to act in both a pro- and antifibrotic capacity, as well as their ability to regulate the activation of resident and recruited myofibroblasts, macrophages and the factors they express are integrated into all stages of the fibrotic process. These various, and sometimes opposing, functions may be performed by distinct macrophage subpopulations, the identification of which is a growing focus of fibrosis research. Although collagen-secreting myofibroblasts once were thought of as the master "producers" of fibrosis, this review will illustrate how macrophages function as the master "regulators" of fibrosis. Copyright Thieme Medical Publishers.
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              M1 and M2 Macrophages: Oracles of Health and Disease

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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                17 January 2017
                January 2017
                : 18
                : 1
                : 171
                Affiliations
                The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; lyc@ 123456mskcc.org (C.L.L.); katarur@ 123456mskcc.org (R.P.K.)
                Author notes
                [* ]Correspondence: mehrarab@ 123456mskcc.org ; Tel.: +1-212-639-8639; Fax: +1-212-717-3677
                Article
                ijms-18-00171
                10.3390/ijms18010171
                5297803
                28106728
                47fb3d94-351d-4a6a-9eae-06aaeec02778
                © 2017 by the authors; 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
                : 25 October 2016
                : 12 January 2017
                Categories
                Review

                Molecular biology
                lymphedema,inflammatory skin conditions,inflammatory cells,immunity
                Molecular biology
                lymphedema, inflammatory skin conditions, inflammatory cells, immunity

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