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Human IgA Fc receptor FcαRI (CD89) triggers different forms of neutrophil death depending on the inflammatory microenvironment
- Source :
- Journal of immunology (Baltimore Md. : 1950), Journal of Immunology
- Publication Year :
- 2014
-
Abstract
- 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.
- Subjects :
- medicine.drug_class
MAP Kinase Signaling System
Neutrophils
Immunology
Fc receptor
Stimulation
Receptors, Fc
Biology
Monoclonal antibody
Sepsis
03 medical and health sciences
Phosphatidylinositol 3-Kinases
0302 clinical medicine
Antigens, CD
medicine
Immunology and Allergy
Humans
PI3K/AKT/mTOR pathway
Cells, Cultured
030304 developmental biology
0303 health sciences
Cell Death
Macrophages
Toll-Like Receptors
Antibodies, Monoclonal
medicine.disease
In vitro
Coculture Techniques
Immunity, Innate
3. Good health
Cell biology
Vacuolization
Cellular Microenvironment
Apoptosis
biology.protein
Cytokines
Inflammation Mediators
030215 immunology
Subjects
Details
- ISSN :
- 15506606
- Volume :
- 193
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.doi.dedup.....f211b94a9377bdbd2959c63783c3bd9f