INFLAMMATORY AND IMMUNE-RESPONSES ARE IMPAIRED IN MICE DEFICIENT IN INTERCELLULAR-ADHESION MOLECULE-1

Gene targeting was used to produce mice deficient in intercellular adh esion molecule 1 (ICAM-1) or CD54, an immunoglobulin-like cell adhesio n molecule that binds beta2 integrins. Homozygous deficient animals de velop normally, are fertile, and have a moderate granulocytosis. The n ature of the mutation, RNA analysis, and immunostaining are consistent with complete loss of surface expression of ICAM-1. Deficient mice ex hibit prominent abnormalities of inflammatory responses including impa ired neutrophil emigration in response to chemical peritonitis and dec reased contact hypersensitivity to 2,4-dinitrofluorobenzene. Mutant ce lls provided negligible stimulation in the mixed lymphocyte reaction, although they proliferated normally as responder cells. These mutant a nimals will be extremely valuable for examining the role of ICAM-1 and its counterreceptors in inflammatory disease processes and atheroscle rosis.