An Explorative Approach to Examining the Role of Ischemia and Inflammation on the Function of Autoantibodies Against G Protein–Coupled Receptors and Their Corresponding Agonists

Wallukat G, Lakatos P, Steinhorst K, Flecks M, Hohberger B (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Book Volume: 27

Article Number: 2797

Journal Issue: 6

DOI: 10.3390/ijms27062797

Abstract

Autoantibodies (AAbs) play an important role in the development of autoimmune diseases. While many AAbs induce apoptosis of target cells, a distinct subgroup, termed functional autoantibodies (fAAbs) against G protein–coupled receptors (GPCRs), can modulate physiological receptor signaling without inducing cell death. The functional activity of GPCR-fAAbs may be influenced by various cofactors, including inflammation (e.g., inflammatory cytokine, ciliary neurotrophic factor (CNTF)) and ischemia. As ischemia triggers a substantial release of arachidonic acid (AA) from membrane phospholipids, the present study aimed to examine exploratively the influence of AA, eicosapentaenoic acid (EPA), and CNTF on the responses of spontaneously beating neonatal rat cardiomyocytes to GPCR agonists and GPCR-fAAbs. AA and EPA differentially influenced responses in cardiomyocytes induced by GPCR-fAAbs: AA altered the functional responses associated with adrenergic β2-fAAb, adrenergic α1-fAAb, angiotensin II (AT1)-fAAb, endothelin A (ETA)-fAAb and angiotensin 1–7 MAS-fAAbs. However, muscarinergic M2-fAAb responses remained largely unaffected. In contrast, EPA attenuated the responses to β2-fAAb, α1-fAAb, AT1-fAAb, and ETA-fAAb, while MAS-fAAb and M2-fAAb responses were not markedly altered. CNTF acted as a time-dependent modulator of cardiomyocyte chronotropic responses and influenced the magnitude of GPCR-mediated signaling on a cardiomyocyte bioassay. Together, these findings might suggest that lipid mediators such as AA and EPA or CNTF may modulate functional responses of cardiomyocytes associated with GPCR-fAAbs.

Authors with CRIS profile

Involved external institutions

Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft / Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) Germany (DE)

How to cite

APA:

Wallukat, G., Lakatos, P., Steinhorst, K., Flecks, M., & Hohberger, B. (2026). An Explorative Approach to Examining the Role of Ischemia and Inflammation on the Function of Autoantibodies Against G Protein–Coupled Receptors and Their Corresponding Agonists. International Journal of Molecular Sciences, 27(6). https://doi.org/10.3390/ijms27062797

MLA:

Wallukat, Gerd, et al. "An Explorative Approach to Examining the Role of Ischemia and Inflammation on the Function of Autoantibodies Against G Protein–Coupled Receptors and Their Corresponding Agonists." International Journal of Molecular Sciences 27.6 (2026).

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