Propionibacterium acnes-induced hepatic granuloma formation is impaired in mice lacking tetraspanin CD9.
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-gamma, 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.
Yamane
Hiroyuki
H
Department of Molecular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
Tachibana
Isao
I
Takeda
Yoshito
Y
Saito
Yoshiyuki
Y
Tamura
Yoshio
Y
He
Ping
P
Suzuki
Mayumi
M
Shima
Yoshihito
Y
Yoneda
Tsutomu
T
Hoshino
Shigenori
S
Inoue
Koji
K
Kijima
Takashi
T
Yoshida
Mitsuhiro
M
Kumagai
Toru
T
Osaki
Tadashi
T
Eishi
Yoshinobu
Y
Kawase
Ichiro
I
D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D002460:Cell Line; D045744:Cell Line, Tumor; D002633:Chemotaxis / Q000276:immunology; D006099:Granuloma / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D007150:Immunohistochemistry / Q000379:methods; D007371:Interferon-gamma / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000382:microbiology; D008107:Liver Diseases / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000032:analysis*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011425:Propionibacterium acnes; D060245:Tetraspanin 29; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D015703:Antigens, CD; C554870:Cd9 protein, mouse; D008562:Membrane Glycoproteins; D060245:Tetraspanin 29; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma