Propionibacterium acnes-induced hepatic granuloma formation is impaired in mice lacking tetraspanin CD9

Authors: Yamane, Hiroyuki¹; Tachibana, Isao¹; Takeda, Yoshito¹; Saito, Yoshiyuki¹; Tamura, Yoshio¹; He, Ping¹; Suzuki, Mayumi¹; Shima, Yoshihito¹; Yoneda, Tsutomu¹; Hoshino, Shigenori¹; Inoue, Koji¹; Kijima, Takashi¹; Yoshida, Mitsuhiro¹; Kumagai, Toru¹; Osaki, Tadashi¹; Eishi, Yoshinobu²; Kawase, Ichiro¹

Source: The Journal of Pathology, Volume 206, Number 4, August 2005 , pp. 486-492(7)

Publisher: John Wiley & Sons, Ltd.

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Abstract:

The granuloma is a host defence response to persistent pathogenic irritants. In the process of granuloma formation, the activation, migration, and fusion of macrophages occur locally, but the mechanisms involved remain elusive. Tetraspanins regulate cell migration and fusion by organizing functional molecular complexes in membrane microdomains. Here we investigated the role of tetraspanin CD9 in hepatic granuloma formation. Immunostaining of the liver of untreated wild-type mice showed that CD9 was expressed by vascular endothelial cells and perivenular hepatocytes. When intrahepatic granulomas were induced by intravenous injection of Propionibacterium acnes, hepatocyte CD9 was extensively upregulated, while inflammatory cells constituting granulomas were mostly negative for CD9. Compared with wild-type littermates, CD9-knockout mice showed dissemination of Propionibacterium acnes and reduced number and size of granulomas after the injection. Moreover, production of granuloma-inducing cytokines, TNF- alpha

and IFN-

, was delayed and chemotactic activity for macrophages was suppressed in the liver of mutant mice. These results suggest that CD9 is one of the proteins that promotes granuloma formation in the liver. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Keywords: adhesion molecules; inflammation; monocytes/macrophages; transgenic/knockout mice

Document Type: Research article

DOI: http://dx.doi.org/10.1002/path.1793

Affiliations: 1: Department of Molecular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan 2: Department of Human Pathology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan

Publication date: 2005-08-01

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Propionibacterium acnes-induced hepatic granuloma formation is impaired in mice lacking tetraspanin CD9

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