Reduced susceptibility to collagen-induced arthritis in mice deficient in intercellular adhesion molecule-1.
Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the firm adhesion of leukocytes to venular endothelium and facilitates leukocyte extravasation from the vasculature into inflamed tissue. In addition, ICAM-1 is an important costimulatory molecule during Ag presentation to lymphocytes. Using mice deficient in ICAM-1, we have investigated the role of this molecule in the development of collagen-induced arthritis. After immunization with type II collagen, 71% of wild-type mice developed arthritis compared with 50% of ICAM-1 heterozygote mutants and 18% of ICAM-1 homozygous mutants. In those ICAM-1 mutants that developed arthritis, the mean day of onset, the mean number of involved paws, and the severity of paw inflammation were not significantly different from those in wild-type mice. The reduced incidence of arthritis in the ICAM-1 homozygous mutant mice was not due to lack of immunity to type II collagen, since these mice developed similar levels of anti-type II collagen IgG compared with wild-type mice and had a positive delayed-type hypersensitivity reaction to type II collagen. The reduction of arthritis in heterozygous as well as homozygous deficient mice indicates that expression of ICAM-1 can be a pivotal variable in the pathogenesis of collagen-induced arthritis in mice. The results suggest that naturally occurring genetic variation in the expression of ICAM-1 or related inflammatory cell adhesion molecules might influence susceptibility to the complex disease of rheumatoid arthritis in humans and support the concept that pharmacologic approaches to chronic reduction in the expression or the function of ICAM-1 may be of therapeutic value.
Bullard
D C
DC
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Hurley
L A
LA
Lorenzo
I
I
Sly
L M
LM
Beaudet
A L
AL
Staite
N D
ND
D000818:Animals; D017951:Antigen Presentation; D001168:Arthritis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000235:genetics; D002448:Cell Adhesion; D003094:Collagen / Q000276:immunology*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D006968:Hypersensitivity, Delayed / Q000276:immunology; D016867:Immunocompromised Host; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D007958:Leukocyte Count; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout
D007074:Immunoglobulin G; D018799:Intercellular Adhesion Molecule-1; D003094:Collagen