ICAM-1-dependent pathway is critically involved in the pathogenesis of adjuvant arthritis in rats.
Intercellular adhesion molecule 1 (ICAM-1) plays important roles in immune responses. In order to examine whether ICAM-1 is involved in pathogenesis of adjuvant arthritis (AA), we investigated the effect of anti-ICAM-1 mAb, 1A29, on AA in rats. In vivo administration of 1A29 exerted a very strong suppressive effect on the development of arthritis and induced a marked reduction of inflammatory parameters. 1A29 suppressed the Ag-specific proliferative response of lymph node cells from AA rats, suggesting that the mAb blocked the Ag recognition phase. The study using adoptive transfer of AA revealed that 1A29 completely inhibited production of arthritogenic lymphocytes in donors and partially suppressed progression of arthritis in recipients caused by these lymphocytes. These findings indicated that the inhibitory effect of 1A29 on development of arthritis was at least twofold, i.e., 1) interference with cell-cell interaction between APC and T cells, which resulted in abrogation of effector cell generation; and 2) blocking of effector cell migration to inflammatory lesions. These results indicated that ICAM-1-dependent pathway is critically involved in the pathogenesis of AA. The data support the concept that ICAM-1-dependent pathways are important in chronic inflammatory disease.
Exploratory Research Laboratory 3, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Y
Y
Iigo
T
T
Takashi
T
T
Tamatani
M
M
Miyasaka
T
T
Higashida
H
H
Yagita
K
K
Okumura
W
W
Tsukada
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001169:Arthritis, Experimental / Q000209:etiology*; D001799:Blood Sedimentation; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D005260:Female; D016219:Immunotherapy, Adoptive; D018799:Intercellular Adhesion Molecule-1; D051379:Mice; D009504:Neutrophils / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D018799:Intercellular Adhesion Molecule-1