Distinct inflammatory properties of late-activated macrophages in inflammatory myopathies.
Distinct mechanisms such as humeral immunity in dermatomyositis (DM) and T-cell-mediated cytotoxicity in polymyositis (PM) contribute to the pathology of inflammatory myopathies. In addition, different subsets of macrophages are present in both diseases. Herein, the characteristics of 25F9-positive macrophages in skeletal muscle inflammation are outlined. Muscle biopsies of subjects with DM and PM were studied by immunohistochemical multi-labelling using the late-activation marker 25F9, together with markers characterizing macrophage function including IFN-gamma, iNOS, and TGF-beta. In PM, a robust expression of IFN-gamma, iNOS, and TGF-beta was observed in inflammatory cells. Double- and serial-labelling revealed that a subset of 25F9-positive macrophages in the vicinity of injured muscle fibres expressed iNOS and TGF-beta, but not IFN-gamma. In DM, IFN-gamma, iNOS and TGF-beta were also expressed in inflammatory cells in the endomysium. Double- and serial-labelling studies in DM indicated that 25F9-positive macrophages expressed TGF-beta and to a lesser degree iNOS, but not IFN-gamma. In conclusion, our data suggest that late-activated macrophages contribute to the pathology of inflammatory myopathies.
Department of Pediatrics, Division of Pediatric Neurology, Medical University of Innsbruck, Austria. Kevin.Rostasy@uki.at
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Rostasy
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Schmidt
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Bahn
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Pfander
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Piepkorn
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Wilichowski
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Schulz-Schaeffer
D000328:Adult; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002648:Child; D003882:Dermatomyositis / Q000503:physiopathology*; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism / Q000502:physiology; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism / Q000502:physiology; D017285:Polymyositis / Q000503:physiopathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology
C472507:25F9 antigen, human; D015214:Antigens, Differentiation, Myelomonocytic; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II