Acceleration and increased severity of collagen-induced arthritis in P-selectin mutant mice.
P-selectin plays an important role in leukocyte adherence to microvascular endothelium and is expressed in synovial tissue from patients with rheumatoid arthritis (RA). However, the contribution of P-selectin to the initiation and chronicity of joint inflammation is not well understood. In these studies, collagen-induced arthritis (CIA) was induced in P-selectin mutant (-/-) mice to explore the role of P-selectin in the development of joint inflammation. Surprisingly, CIA onset was accelerated and severity was increased in P-selectin mutant mice, compared with wild-type mice (+/+). Increased levels of anti-type II collagen IgG were detected in both nonarthritic and arthritic P-selectin mutant mice from days 14-91. In addition, splenocytes isolated from immunized and nonimmunized P-selectin mutant mice produced significantly less IL-2 and IL-4, but significantly higher levels of IL-10 and IL-5 than splenocytes from wild-type mice. These observations show that P-selectin-mediated leukocyte rolling is not required for the development of murine CIA and that P-selectin expression exerts a controlling effect on the development of Ag-driven inflammatory joint disease, possibly by mediating the recruitment and/or trafficking of specific leukocyte subtypes into lymphoid tissue or inflammatory foci.
Bullard
D C
DC
Department of Comparative Medicine, University of Alabama, Birmingham 35294, USA. pike@uab.edu
Mobley
J M
JM
Justen
J M
JM
Sly
L M
LM
Chosay
J G
JG
Dunn
C J
CJ
Lindsey
J R
JR
Beaudet
A L
AL
Staite
N D
ND
D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology* / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood; D003094:Collagen / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D018450:Disease Progression; D005260:Female; D005552:Forelimb; D006614:Hindlimb; D015994:Incidence; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019007:P-Selectin / Q000235:genetics*; D012720:Severity of Illness Index; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014955:Wrist Joint / Q000473:pathology
D001323:Autoantibodies; D016207:Cytokines; D019007:P-Selectin; D003094:Collagen