Human IgA Fc receptor FcαRI (CD89) triggers different forms of neutrophil death depending on the inflammatory microenvironment

Wehrli, Marc; Cortinas-Elizondo, Fabiola; Hlushchuk, Ruslan; Daudel, Fritz; Villiger, Peter M.; Miescher, Sylvia; Zuercher, Adrian W.; Djonov, Valentin; Simon, Hans-Uwe; von Gunten, Stephan (2014). Human IgA Fc receptor FcαRI (CD89) triggers different forms of neutrophil death depending on the inflammatory microenvironment. Journal of immunology, 193(11), pp. 5649-5659. American Association of Immunologists 10.4049/​jimmunol.1400028

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FcαRI (CD89), the human Fc receptor for IgA, is highly expressed on neutrophil granulocytes. In this study, we show that FcαRI induces different forms of neutrophil death, depending on the inflammatory microenvironment. The susceptibility of inflammatory neutrophils from sepsis or rheumatoid arthritis toward death induced by specific mAb, or soluble IgA at high concentrations, was enhanced. Although unstimulated cells experienced apoptosis following anti-FcαRI mAb stimulation, preactivation with cytokines or TLR agonists in vitro enhanced FcαRI-mediated death by additional recruitment of caspase-independent pathways, but this required PI3K class IA and MAPK signaling. Transmission electron microscopy of FcαRI-stimulated cells revealed cytoplasmic changes with vacuolization and mitochondrial swelling, nuclear condensation, and sustained plasma membrane. Coculture experiments with macrophages revealed anti-inflammatory effects of the partially caspase-independent death of primed cells following FcαRI engagement. Our data suggest that FcαRI has the ability to regulate neutrophil viability and to induce different forms of neutrophils depending on the inflammatory microenvironment and specific characteristics of the ligand-receptor interactions. Furthermore, these findings have potential implications for FcαRI-targeted strategies to treat neutrophil-associated inflammatory diseases.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology
04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic of Intensive Care
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Wehrli, Marc; Schorer, Myriam Fabiola; Hlushchuk, Ruslan; Daudel, Fritz; Villiger, Peter; Djonov, Valentin; Simon, Hans-Uwe and von Gunten, Stephan

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0022-1767

Publisher:

American Association of Immunologists

Language:

English

Submitter:

Anita Dähler

Date Deposited:

19 Jan 2015 10:44

Last Modified:

10 Sep 2017 07:58

Publisher DOI:

10.4049/​jimmunol.1400028

PubMed ID:

25339672

BORIS DOI:

10.7892/boris.61962

URI:

https://boris.unibe.ch/id/eprint/61962

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