TY - JOUR
T1 - CD44 involvement in experimental collagen-induced arthritis (CIA)
AU - Nedvetzki, Shlomo
AU - Walmsley, Marita
AU - Alpert, Evgenya
AU - Williams, Richard O.
AU - Feldmann, Marc
AU - Naor, David
PY - 1999/8
Y1 - 1999/8
N2 - CD44 is a pro-inflammatory cell surface molecule that supports cell migration and cell lodgment in target organs. Therefore, CD44 targeting with specific monoclonal antibodies (mAbs) should be useful for the inhibition of collagen-induced arthritis (CIA) as well as other autoimmune diseases that are dependent on inflammatory cells. In the present paper, we confirm and expand previous reports showing the anti-arthritogenic effect of anti-CD44 mAbs directed against constant epitopes of the CD44 receptor. We demonstrate that such anti-CD44 mAbs can induce resistance to CIA after disease onset. Even accelerated disease developed after two injections of type II collagen was markedly inhibited by IM7.8.1 anti-CD44 mAb. Although KM81 anti-CD44 mAb is a less efficient anti-arthritogenic reagent than IM7.8.1, its Fab' fragments partially inhibit CIA. This finding implies that the antibody blocks CD44 function rather than modulating CD44 cell surface expression or mediating Fc-dependent activities. Histopathological analysis revealed that the anti-CD44 mAb markedly reduces the synovial inflammatory cellular response and the consequent damage to the joint. As CD44 is an alternatively spliced multistructural molecule, similar anti-arthritogenic effects may be achieved by mAbs directed against CD44 isoforms expressed on the pathological cells in question, but not on normal cells, thus leaving the physiological functions intact.
AB - CD44 is a pro-inflammatory cell surface molecule that supports cell migration and cell lodgment in target organs. Therefore, CD44 targeting with specific monoclonal antibodies (mAbs) should be useful for the inhibition of collagen-induced arthritis (CIA) as well as other autoimmune diseases that are dependent on inflammatory cells. In the present paper, we confirm and expand previous reports showing the anti-arthritogenic effect of anti-CD44 mAbs directed against constant epitopes of the CD44 receptor. We demonstrate that such anti-CD44 mAbs can induce resistance to CIA after disease onset. Even accelerated disease developed after two injections of type II collagen was markedly inhibited by IM7.8.1 anti-CD44 mAb. Although KM81 anti-CD44 mAb is a less efficient anti-arthritogenic reagent than IM7.8.1, its Fab' fragments partially inhibit CIA. This finding implies that the antibody blocks CD44 function rather than modulating CD44 cell surface expression or mediating Fc-dependent activities. Histopathological analysis revealed that the anti-CD44 mAb markedly reduces the synovial inflammatory cellular response and the consequent damage to the joint. As CD44 is an alternatively spliced multistructural molecule, similar anti-arthritogenic effects may be achieved by mAbs directed against CD44 isoforms expressed on the pathological cells in question, but not on normal cells, thus leaving the physiological functions intact.
KW - Adhesion molecules
KW - Arthritis
KW - Autoimmunity
KW - CD44
KW - Inflammation
UR - http://www.scopus.com/inward/record.url?scp=0032791517&partnerID=8YFLogxK
U2 - 10.1006/jaut.1999.0294
DO - 10.1006/jaut.1999.0294
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 10441166
AN - SCOPUS:0032791517
SN - 0896-8411
VL - 13
SP - 39
EP - 47
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
IS - 1
ER -