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Published online before print February 13, 2007

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(Journal of Leukocyte Biology. 2007;81:1197-1204.)
© 2007 by Society for Leukocyte Biology

Intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 cooperatively contribute to the cutaneous Arthus reaction

Hidemitsu Orito^*, Manabu Fujimoto^*,1, Nobuko Ishiura, Koichi Yanaba^*, Takashi Matsushita^*, Minoru Hasegawa^*, Fumihide Ogawa, Kazuhiko Takehara^* and Shinichi Sato

^* Department of Dermatology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan;
Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan; and
Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

¹ Correspondence: Department of Dermatology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan. E-mail: fujimoto-m{at}umin.ac.jp

ABSTRACT

Immune complex (IC)-induced inflammation is mediated by inflammatory cell infiltration, a process that is highly regulated by expression of multiple adhesion molecules. The roles and interactions of ICAM-1 and VCAM-1, the major regulators of leukocyte firm adhesion, were examined in the cutaneous reverse-passive Arthus reaction using ICAM-1-deficient (ICAM-1^–/–) mice and blocking mAb against VCAM-1. Within 8 h, IC challenge of wild-type mice induced edema, hemorrhage, interstitial accumulation of neutrophils and mast cells, as well as production of TNF- and IL-6. All of these inflammatory parameters were reduced significantly in ICAM-1^–/– mice. The blockade of VCAM-1 in wild-type mice did not affect any inflammatory parameters. In contrast, ICAM-1^–/– mice treated with anti-VCAM-1 mAb had significantly reduced edema, hemorrhage, and neutrophil infiltration. Furthermore, VCAM-1 blockade in ICAM-1^–/– mice suppressed cutaneous TNF- and IL-6 production. Thus, VCAM-1 plays a complementary role to ICAM-1 in the cutaneous Arthus reaction by regulating leukocyte accumulation and proinflammatory cytokine production.

Key Words: cell adhesion molecule • VLA-4 • neutrophil • vasculitis

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