The inhibitory co-receptor, PECAM-1 provides a protective effect in suppression of collagen-induced arthritis.
Studies of PECAM-1(-/-) mice have identified that PECAM-1 functions as an inhibitory co-receptor to modulate immunological responsiveness. In this study, we describe the in vivo consequences of PECAM-1 deficiency in mouse models of collagen-induced arthritis (CIA) and K/BxN passive transfer model that resembles many of the features of human rheumatoid arthritis. Immunization of PECAM-1(-/-) C57BL/6 (H-2b) mice with chicken collagen type II induced CIA with an incidence of 82% by day 49, while 33%; of wild-type and 100% of DBA/1 mice developed arthritis in a similar time frame. The mean onset of disease for PECAM-1(-/-) C57BL/6 mice was day 32 compared to day 51 for wild-type C57BL/6 mice and day 18 for DBA/1 mice (H-2q susceptible). In terms of disease severity, the mean maximal arthritic index for PECAM-1(-/-) C57BL/6 mice was comparable to DBA/1 mice (8.91 +/- 0.91 vs 11.67 +/- 0.82). This mean maximal index in PECAM-1(-/-) C57BL/6 mice was significantly higher than wild-type C57BL/6 mice (5.00 +/- 0.73). IgG1 and IgG2b antibody responses against CII were elevated in arthritic PECAM-1(-/-) C57BL/6 mice compared to wild-type C57BL/6 mice. Histological examination of arthritic paws of PECAM-1(-/-) C57BL/6 mice revealed inflammatory infiltrates of lymphocytic/monocytic cells and cartilage/bone destruction similar to CIA-induced DBA/1 arthritic paws. In the K/BxN model, the arthritis was not augmented in PECAM-1(-/-) mice compared to wild-type mice. In contrast, in active CIA, PECAM-1(-/-) mice developed severe disease comparable to susceptible DBA/1 mice and profoundly more severe than C57BL/6 mice, where only one third developed a mild/moderate disease. Together these observations suggest that PECAM-1 plays a crucial role in the suppression of development of autoimmune arthritis.
Wong
Mae-Xhum
MX
Austin Research Institute, Austin Hospital, Heidelberg, Victoria, Australia.
Hayball
John D
JD
Hogarth
P Mark
PM
Jackson
Denise E
DE
D019264:Adoptive Transfer; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002356:Cartilage / Q000473:pathology; D024043:Collagen Type II / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology*
D024043:Collagen Type II; D019408:Platelet Endothelial Cell Adhesion Molecule-1
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