Immune complex-induced apoptosis and concurrent immune complex clearance are anti-inflammatory neutrophil functions

• Published in: Cell death & disease Vol. 12; no. 4; p. 296
• Main Authors: Karmakar, Utsa, Chu, Julia Y., Sundaram, Kruthika, Astier, Anne L., Garside, Hannah, Hansen, Carsten G., Dransfield, Ian, Vermeren, Sonja
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.03.2021; Springer Nature B.V; Nature Publishing Group
• Subjects: 13/2; 13/95; 14; 14/19; 631/250/1933; 631/250/2504/223/1699; 631/80/313/1461; 631/80/82/23; 82/1; 96/31; 96/63; Antibodies; Antigen-Antibody Complex - metabolism; Antigen-antibody complexes; Apoptosis; Autoimmune diseases; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell Culture; Cell death; Humans; Immune clearance; Immunology; Inflammation; Inflammation - immunology; Internalization; Leukocytes (neutrophilic); Life Sciences; Neutrophils; Neutrophils - immunology; Phagocytosis; Reactive oxygen species
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-021-03528-8

Persistent neutrophilic inflammation drives host damage in autoimmune diseases that are characterized by abundant immune complexes. Insoluble immune complexes (iICs) potently activate pro-inflammatory neutrophil effector functions. We and others have shown that iICs also promote resolution of inflammation via stimulation of neutrophil apoptosis. We demonstrate here that iICs trigger FcγRIIa-dependent neutrophil macropinocytosis, leading to the rapid uptake, and subsequent degradation of iICs. We provide evidence that concurrent iIC-induced neutrophil apoptosis is distinct from phagocytosis-induced cell death. First, uptake of iICs occurs by FcγRII-stimulated macropinocytosis, rather than phagocytosis. Second, production of reactive oxygen species, but not iIC-internalization is a pre-requisite for iIC-induced neutrophil apoptosis. Our findings identify a previously unknown mechanism by which neutrophils can remove pro-inflammatory iICs from the circulation. Together iIC clearance and iIC-induced neutrophil apoptosis may act to prevent the potential escalation of neutrophilic inflammation in response to iICs.