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

Utsa Karmakar, Julia Chu, Kruthika Sundaram, Anne Astier, Hannah Garside, Carsten Gram Hansen, Ian Dransfield, Sonja Vermeren

Research output: Contribution to journalArticlepeer-review

Abstract

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 FcRIIa-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 FcRII-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.
Original languageEnglish
JournalCell Death and Disease
DOIs
Publication statusPublished - 19 Mar 2021

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