Inflammatory and immune responses are impaired in mice deficient in intercellular adhesion molecule 1.

TLDR

The study aims to use ICAM‑1–deficient mice to investigate ICAM‑1’s role in inflammation and atherosclerosis. ICAM‑1–deficient mice were generated by gene targeting of the ICAM‑1 (CD54) locus. ICAM‑1–deficient mice develop normally but exhibit complete loss of ICAM‑1 surface expression, moderate granulocytosis, impaired neutrophil migration, reduced contact hypersensitivity, and defective lymphocyte stimulation.

Abstract

Gene targeting was used to produce mice deficient in intercellular adhesion molecule 1 (ICAM-1) or CD54, an immunoglobulin-like cell adhesion molecule that binds beta 2 integrins. Homozygous deficient animals develop normally, are fertile, and have a moderate granulocytosis. The nature of the mutation, RNA analysis, and immunostaining are consistent with complete loss of surface expression of ICAM-1. Deficient mice exhibit prominent abnormalities of inflammatory responses including impaired neutrophil emigration in response to chemical peritonitis and decreased contact hypersensitivity to 2,4-dinitrofluorobenzene. Mutant cells provided negligible stimulation in the mixed lymphocyte reaction, although they proliferated normally as responder cells. These mutant animals will be extremely valuable for examining the role of ICAM-1 and its counterreceptors in inflammatory disease processes and atherosclerosis.