Acceleration of the onset of collagen-induced arthritis by a deficiency of platelet endothelial cell adhesion molecule 1.
OBJECTIVE
Platelet endothelial cell adhesion molecule 1 (PECAM-1; CD31) is a member of the immunoglobulin superfamily that is expressed in platelets, leukocytes, and endothelial cells. PECAM-1 has been shown to play a role in transendothelial migration of leukocytes and contains immunoreceptor tyrosine-based inhibitory motifs in its cytoplasmic tail and inhibits cellular responses. We examined the role of PECAM-1 in the development of collagen-induced arthritis (CIA).


METHODS
CIA was induced in PECAM-1-deficient DBA/1 mice. The incidence of arthritis and the arthritis index were examined. Anti-type II collagen (anti-CII) antibody levels and interferon-gamma (IFNgamma) production by lymph node cells and spleen cells were determined. Lymphocytes from arthritic PECAM-1-deficient and wild-type mice were labeled with dye, transferred to arthritic PECAM-1(+/-) mice, and cell migration to inflamed joints was examined.


RESULTS
PECAM-1-deficient mice showed accelerated onset of arthritis and increased severity only during the early phase. Anti-CII antibody levels were also increased during the early phase. IFNgamma production by lymph node cells and spleen cells from PECAM-1-deficient mice in response to CII was higher than that in wild-type mice. Lymphocytes from arthritic PECAM-1-deficient mice showed accelerated migration to inflamed joints, but not lymph nodes or spleen. The development of anti-CII antibody-induced arthritis was similar in PECAM-1-deficient and wild-type mice.


CONCLUSIONS
These results indicate that PECAM-1 negatively regulates humoral and cell-mediated immune responses and lymphocyte migration into joints and, consequently, the development of CIA. In addition, the role of PECAM-1 in the transendothelial migration of leukocytes appears to be redundant in this model.
Tada
Yoshifumi
Y
Saga Medical School, Saga, Japan. taday@post.saga-med.ac.jp
Koarada
Syuichi
S
Morito
Fumitaka
F
Ushiyama
Osamu
O
Haruta
Yoshio
Y
Kanegae
Futoshi
F
Ohta
Akihide
A
Ho
Alexandra
A
Mak
Tak W
TW
Nagasawa
Kohei
K
D019264:Adoptive Transfer; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001323:Autoantibodies / Q000097:blood; D002465:Cell Movement; D024043:Collagen Type II / Q000276:immunology / Q000494:pharmacology; D004195:Disease Models, Animal; D006614:Hindlimb / Q000473:pathology; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D007596:Joints / Q000473:pathology; D008198:Lymph Nodes / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies; D024043:Collagen Type II; D007074:Immunoglobulin G; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D007371:Interferon-gamma