Intercellular Adhesion Molecule 1 Functions as an Efferocytosis Receptor in Inflammatory Macrophages

Hannah L. Wiesolek, Triet M. Bui, Joseph J. Lee, Prarthana Dalal, Ariel Finkielsztein, Ayush Batra, Edward B. Thorp, Ronen Sumagin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Intercellular adhesion molecule-1 (ICAM-1) is up-regulated during inflammation by several cell types. ICAM-1 is best known for its role in mediating leukocyte adhesion to endothelial cells and guiding leukocytes across the vascular wall. Recently, macrophages have been shown to express ICAM-1, however, their role in macrophage function is unclear. We found that ICAM-1 expression was induced during inflammatory macrophage polarization and high numbers of ICAM-1–expressing macrophages were noted in inflamed colon tissue in a murine colitis model and in human inflammatory bowel disease. Because tissue macrophages play a critical role in removing apoptotic/necrotic cells in inflammation and injury, a process termed efferocytosis, it was examined whether ICAM-1 contributes to this process. Genetic deletion (ICAM-1 knockout mice) or siRNA-mediated knockdown of ICAM-1 in isolated murine and human macrophages significantly impaired apoptotic cell (AC) engulfment. Impairment in the engulfment of Jurkat T cells, neutrophils, and epithelial cells was confirmed ex vivo by inflammatory macrophages and in vivo by thioglycolate-recruited peritoneal macrophages. Decreased efferocytosis was also seen in vitro and in vivo with inhibition of ICAM-1 adhesive interactions, using a function blocking anti–ICAM-1 antibody. Mechanistically, it was found that ICAM-1 actively redistributes to cluster around engulfed ACs to facilitate macrophage–AC binding. Our findings define a new role for ICAM-1 in promoting macrophage efferocytosis, a critical process in the resolution of inflammation and restoration of tissue homeostasis.

Original languageEnglish (US)
Pages (from-to)874-885
Number of pages12
JournalAmerican Journal of Pathology
Volume190
Issue number4
DOIs
StatePublished - Apr 2020

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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