Liver-infiltrating T lymphocytes are attracted selectively by IFN-inducible protein-10.
We have demonstrated that interferon-inducible protein-10 (IP-10) is produced in hepatocytes surrounded by infiltrative mononuclear cells in chronic hepatitis. To clarify the role of IP-10 in hepatitis, we examined the chemoattractive activity of IP-10 on liver-infiltrating lymphocytes in experimental animal models of hepatitis. IP-10 was specifically induced in the livers of mice treated intravenously (i.v.) with Con A, while monocyte chemotactic protein-1 (MCP-1) showed a much lower level of induction and neither RANTES nor macrophage inflammatory protein-1alpha (MIP-1alpha) was detected. The liver-infiltrating lymphocytes in Con A-induced hepatitis were attracted only by IP-10, and not by other chemokines such as RANTES, MCP-1 and MIP-1alpha. The chemoattractive effect of IP-10 was dose-dependent and was neutralized by monoclonal antibodies to IP-10. The specific effect of IP-10 on liver-infiltrating lymphocytes was also seen on those obtained from rat livers with fulminant hepatitis induced by sequential treatment with killed Propionibacterium acnes (P. acnes) and LPS. Peripheral blood lymphocytes were slightly attracted by IP-10 as well as RANTES and MIP-1alpha, while hepatic resident lymphocytes were not. On the other hand, thioglycolate-elicited peritoneal macrophages did not respond to IP-10, although they did show a response to RANTES, MCP-1 and MIP-1alpha. These results indicated that IP-10 is a specific chemoattractant for T lymphocytes in the inflammatory liver tissues and may play a specific role in the development of hepatitis.
Tamaru
M
M
Pharmaceutical Frontier Research Laboratories, JT Central Pharmaceutical Research Institute, Yokohama, Kanagawa, Japan.
Nishioji
K
K
Kobayashi
Y
Y
Watanabe
Y
Y
Itoh
Y
Y
Okanoue
T
T
Murai
M
M
Matsushima
K
K
Narumi
S
S
D000818:Animals; D019556:COS Cells; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics / Q000276:immunology*; D005260:Female; D006520:Hepatitis, Animal / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008099:Liver / Q000166:cytology* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma