Judith Rademacher1, Angela Kill1, Kathrin Mattat1, Duska Dragun1, Elise Siegert1, Jeannine Günther1, Gabriela Riemekasten2. 1. From the Department of Rheumatology and Clinical Immunology, and the Department of Nephrology, Transplantology and Intensive Care, University Hospital Charité; Cell Autoimmunity, German Rheumatism Research Center (DRFZ), a Leibniz Institute, Berlin; Department of Rheumatology, University of Lübeck, Lübeck, Germany.J. Rademacher, MD, Department of Rheumatology and Clinical Immunology, Charité University Hospital, and Cell Autoimmunity, DRFZ; A. Kill, MD, Department of Rheumatology and Clinical Immunology, Charité University Hospital, and Cell Autoimmunity, DRFZ; K. Mattat, Department of Rheumatology and Clinical Immunology, Charité University Hospital; D. Dragun, Professor, Department of Nephrology, Transplantology and Intensive Care, University Hospital Charité; E. Siegert, MD, Department of Rheumatology and Clinical Immunology, Charité University Hospital; J. Günther*, MSc, Department of Rheumatology and Clinical Immunology, Charité University Hospital, and Cell Autoimmunity, DRFZ; G. Riemekasten*, Professor, Department of Rheumatology and Clinical Immunology, Charité University Hospital, and Cell Autoimmunity, DRFZ, and Department of Rheumatology, University of Lübeck. 2. From the Department of Rheumatology and Clinical Immunology, and the Department of Nephrology, Transplantology and Intensive Care, University Hospital Charité; Cell Autoimmunity, German Rheumatism Research Center (DRFZ), a Leibniz Institute, Berlin; Department of Rheumatology, University of Lübeck, Lübeck, Germany.J. Rademacher, MD, Department of Rheumatology and Clinical Immunology, Charité University Hospital, and Cell Autoimmunity, DRFZ; A. Kill, MD, Department of Rheumatology and Clinical Immunology, Charité University Hospital, and Cell Autoimmunity, DRFZ; K. Mattat, Department of Rheumatology and Clinical Immunology, Charité University Hospital; D. Dragun, Professor, Department of Nephrology, Transplantology and Intensive Care, University Hospital Charité; E. Siegert, MD, Department of Rheumatology and Clinical Immunology, Charité University Hospital; J. Günther*, MSc, Department of Rheumatology and Clinical Immunology, Charité University Hospital, and Cell Autoimmunity, DRFZ; G. Riemekasten*, Professor, Department of Rheumatology and Clinical Immunology, Charité University Hospital, and Cell Autoimmunity, DRFZ, and Department of Rheumatology, University of Lübeck. Gabriela.Riemekasten@uksh.de.
Abstract
OBJECTIVE: To assess monocytic expression and ratio of angiotensin and endothelin receptors in systemic sclerosis (SSc) and their functional relevance. METHODS: Receptor expression was measured by flow cytometry. Chemokine ligand 18 (CCL18) concentration in supernatants of peripheral blood mononuclear cells stimulated with immunoglobulin G was measured by ELISA. RESULTS: Monocytes of patients with SSc presented an increased angiotensin II Type 1 receptor (AT1R)/AT2R ratio compared with those of healthy donors. Patients with lung fibrosis and patients with high modified Rodnan skin score showed a reduced endothelin 1 Type A receptor (ETAR)/ETBR ratio. High AT1R/AT2R, but low ETAR/ETBR ratios corresponded to higher CCL18 secretion. CONCLUSION: Altered angiotensin and endothelin receptor ratios observed in SSc influence autoantibody-mediated effects such as secretion of profibrotic CCL18.
OBJECTIVE: To assess monocytic expression and ratio of angiotensin and endothelin receptors in systemic sclerosis (SSc) and their functional relevance. METHODS: Receptor expression was measured by flow cytometry. Chemokine ligand 18 (CCL18) concentration in supernatants of peripheral blood mononuclear cells stimulated with immunoglobulin G was measured by ELISA. RESULTS: Monocytes of patients with SSc presented an increased angiotensin II Type 1 receptor (AT1R)/AT2R ratio compared with those of healthy donors. Patients with lung fibrosis and patients with high modified Rodnan skin score showed a reduced endothelin 1 Type A receptor (ETAR)/ETBR ratio. High AT1R/AT2R, but low ETAR/ETBR ratios corresponded to higher CCL18 secretion. CONCLUSION: Altered angiotensin and endothelin receptor ratios observed in SSc influence autoantibody-mediated effects such as secretion of profibrotic CCL18.
Authors: Ralf J Ludwig; Karen Vanhoorelbeke; Frank Leypoldt; Ziya Kaya; Katja Bieber; Sandra M McLachlan; Lars Komorowski; Jie Luo; Otavio Cabral-Marques; Christoph M Hammers; Jon M Lindstrom; Peter Lamprecht; Andrea Fischer; Gabriela Riemekasten; Claudia Tersteeg; Peter Sondermann; Basil Rapoport; Klaus-Peter Wandinger; Christian Probst; Asmaa El Beidaq; Enno Schmidt; Alan Verkman; Rudolf A Manz; Falk Nimmerjahn Journal: Front Immunol Date: 2017-05-31 Impact factor: 7.561