Inflammatory and immune responses are impaired in mice deficient in intercellular adhesion molecule 1.
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.
Sligh
J E
JE
Institute for Molecular Genetics, Baylor College of Medicine, Houston, TX.
Ballantyne
C M
CM
Rich
S S
SS
Hawkins
H K
HK
Smith
C W
CW
Bradley
A
A
Beaudet
A L
AL
D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002460:Cell Line; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005091:Exons; D005260:Female; D005434:Flow Cytometry; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1; D008070:Lipopolysaccharides / Q000633:toxicity; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains / Q000276:immunology*; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000502:physiology*; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic
D015815:Cell Adhesion Molecules; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; D018799:Intercellular Adhesion Molecule-1