Monocytic Angiotensin and Endothelin Receptor Imbalance Modulate Secretion of the Profibrotic Chemokine Ligand 18.

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.