Naslov
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

Autori
Gunther, J ; Kill, A ; Becker, M ; Radic, M ; Siegert, E ; Riemekasten, G

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
14th Annual European Congress of Rheumatology (EULAR)

Mjesto i datum
Madrid, Španjolska, 12.06.2013. - 15.06.2013

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
AT1R, ETAR, systemic sclerosis

Sažetak
Background Agonistic autoantibodies against the angiotensin II receptor type 1 (AT1R) and the endothelin receptor type A (ETAR) have been identified in patients suffering from systemic sclerosis (SSc). Objectives Here we examined the expression of the AT1R and the ETAR in human immune cells and the pathological effects mediated through these receptors by the corresponding autoantibodies (Aabs). Methods AT1R and ETAR protein expression on peripheral blood T cells, B cells, and monocytes of healthy individuals and SSc patients were analyzed using flow cytometry. Messenger ribonucleic acid (mRNA) expression of both receptors in peripheral blood mononuclear cells (PBMCs) from healthy donors was examined by real-time polymerase chain reaction (PCR). In addition, PBMCs from healthy donors were stimulated in vitro with affinity-purified immunoglobulin G (IgG) fractions from SSc patients containing Aabs against the AT1R and the ETAR, and with IgG from healthy donors serving as control. Alterations in cell surface marker expression, cytokine secretion and chemotactic motility were analyzed using flow cytometry, ELISA, and chemotaxis assays, respectively. Results were correlated with characteristics and clinical findings of the IgG donors. Results Both AT1R and ETAR were expressed on peripheral lymphocytes and monocytes in humans. The protein expression of both receptors was decreased in SSc patients when compared to healthy donors and correlated negatively with disease duration. In addition, IgG fractions of SSc patients containing Aabs against the AT1R and the ETAR induced T cell migration in an anti-AT1R and anti-ETAR Aab level-dependent manner. Moreover, IgG of SSc patients was capable of stimulating PBMCs to produce more IL-8 and CCL18 than IgG of healthy donors. All effects could be significantly abrogated by the application of selective AT1R and ETAR antagonists. Statistical analysis revealed a negative correlation between SSc IgG-induced IL-8 concentrations and disease duration, between SSc IgG-induced CCL18 concentrations and the time since the onset of lung fibrosis as well as an association of CCL18 concentrations with vascular complications of the corresponding SSc IgG donors. Conclusions In this study we demonstrate the expression of both, AT1R and ETAR, on human peripheral T cells, B cells and monocytes. Moreover, we found signs for a chronic activation of peripheral immune cells from SSc patients. The inflammatory and profibrotic effects upon Aab stimulation of PBMCs in vitro, and their associations with clinical findings suggest a role for autoantibody-mediated activation of immune cells mediated through the AT1R and ETAR in the pathogenesis or even the onset of the disease.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA