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(American Journal of Pathology. 2003;163:947-956.)
© 2003 American Society for Investigative Pathology

Expression of Calcium-Binding Proteins MRP8 and MRP14 in Inflammatory Muscle Diseases

Stephan Seeliger^*, Thomas Vogl^*, Ingo Hubert Engels^*, J. Michael Schröder, Clemens Sorg^*, Cord Sunderkötter^* and Johannes Roth^*

From the Institute of Experimental Dermatology,^* the Department of Pediatrics, and the Department of Neuropathology, University Hospital, RWTH-Aachen, Aachen; and the Department of Dermatology and Allergy, University of Ulm, Ulm, Germany

The pathophysiological role of infiltrating macrophages and their subtypes in idiopathic inflammatory myopathies such as dermatomyositis, polymyositis, and inclusion body myositis is not fully clear. Monocytes exhibit various phenotypes with different functional properties such as release of pro- or anti-inflammatory mediators. Expression of myeloid-related proteins MRP8 and MRP14, two calcium-binding S100-proteins, characterizes a proinflammatory subtype of macrophages. We immunohistochemically investigated expression of MRP8 and MRP14 in muscle biopsies of 33 patients with dermatomyositis, polymyositis, and inclusion body myositis. We found a clear association of expression of MRP8 and MRP14 by infiltrating macrophages with degeneration of myofibers. Because MRP8 and MRP14 are secreted by activated macrophages we investigated if these proteins would have direct extracellular effects on myocytes. We found that the purified MRP8/MRP14 complex inhibited proliferation and differentiation of C2C12 myoblasts and that it induced apoptosis via activation of caspase-3 in a time- and dose-dependent manner. These results indicate that in the course of inflammatory myopathies, activated macrophages can promote destruction and impair regeneration of myocytes via secretion of MRP8/MRP14.

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