Angiotensin receptor type 1 and endothelin receptor type A on immune cells mediate migration and the expression of IL-8 and CCL18 when stimulated by autoantibodies from systemic sclerosis patients

• DOI: 10.1186/ar4503
• Publication Date: 2014-03-11T10:01:14Z
• Authors: Jeannine Günther; Angela Kill; Mike Oliver Becker; Harald Heidecke; Judith Rademacher; Elise Siegert; Mislav Radić; Gerd-Rüdiger Burm...; Duska Dragun; Gabriela Riemekasten
• Keywords: CCL18

Abstract Introduction Agonistic autoantibodies (Aabs) against the angiotensin II receptor type 1 (AT1R) and endothelin A (ETAR) have been identified in patients with systemic sclerosis (SSc). In our present study, we examined expression of AT1R ETAR human immune cells pathological effects mediated through these receptors by their corresponding Aabs. Methods Protein on peripheral blood mononuclear (PBMCs) from healthy individuals SSc was analyzed using flow cytometry, mRNA both PBMCs donors real-time PCR. addition, were stimulated vitro affinity-purified immunoglobulin G (IgG) fractions positive for Aabs, as well IgG serving controls. Alterations cell surface marker expression, cytokine secretion chemotactic motility enzyme-linked immunosorbent assays chemotaxis assays, respectively. The results correlated characteristics clinical findings donors. Results Both expressed humans. decreased compared that declined during course disease. Aabs induced T-cell migration an Aab level–dependent manner. Moreover, to produce more interleukin 8 (IL-8) chemokine (C-C motif) ligand 18 (CCL18) than did All significantly reduced selective antagonists. Statistical analysis revealed association SSc-IgG high IL-8 concentrations early disease stage CCL18 lung fibrosis onset vascular complications respective Conclusion could demonstrate T cells, B monocytes. patients, inflammatory profibrotic upon stimulation associations suggest a role Aab-induced activation pathogenesis or even