Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.1203650 on May 3, 2004

Published online before print May 3, 2004
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(Journal of Leukocyte Biology. 2004;76:374-382.)
© 2004 by Society for Leukocyte Biology

P-selectin glycoprotein ligand-1 is required for the development of cutaneous vasculitis induced by immune complex deposition

Koichi Yanaba*,{dagger}, Kazuhiro Komura*, Mayuka Horikawa*, Yukiyo Matsushita*, Kazuhiko Takehara* and Shinichi Sato*,1

* Department of Dermatology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan; and
{dagger} Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan

1Correspondence: Department of Dermatology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan. E-mail: s-sato{at}med.kanazawa-u.ac.jp

Immune complex (IC)-induced tissue injury is mediated by inflammatory cell infiltration that is highly regulated by various adhesion molecules. To assess the contribution of P-selectin glycoprotein ligand-1 (PSGL-1) and selectins in the pathogenetic process, the cutaneous reverse-passive Arthus reaction was examined in mice treated with monoclonal antibodies (mAb) to PSGL-1 or P- and/or E-selectin. Edema and hemorrhage were significantly reduced in mice treated with anti-P-selectin mAb compared with control mice while they were not inhibited in mice treated with anti-E-selectin mAb. It is remarkable that blocking PSGL-1 by mAb resulted in significant, further reduction in edema and hemorrhage compared with blocking anti-P- or anti-E-selectin. However, blockade of E- and P-selectins exhibited more significant reduction relative to PSGL-1 blockade. The inhibited edema and hemorrhage paralleled reduced infiltration of neutrophils and mast cells. Reduced infiltration of neutrophils and mast cells was observed in the peritoneal Arthus reaction and was associated with the decreased production of tumor necrosis factor {alpha} and interleukin-6. The results of this study indicate that PSGL-1 contributes to the Arthus reaction mainly as a ligand of P-selectin and partly as a ligand of E- and/or L-selectin by regulating neutrophil and mast-cell recruitment and that PSGL-1 would be a therapeutic target for human IC-mediated diseases.

Key Words: adhesion molecules • inflammation • mast cells • skin




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H. Orito, M. Fujimoto, N. Ishiura, K. Yanaba, T. Matsushita, M. Hasegawa, F. Ogawa, K. Takehara, and S. Sato
Intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 cooperatively contribute to the cutaneous Arthus reaction
J. Leukoc. Biol., May 1, 2007; 81(5): 1197 - 1204.
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