Role of IP-10/CXCL10 in the progression of pancreatitis-like injury in mice after murine retroviral infection.
Exocrinopathy and pancreatitis-like injury were developed in C57BL/6 (B6) mice infected with LP-BM5 murine leukemia virus, which is known to induce murine acquired immunodeficiency syndrome (MAIDS). The role of chemokines, especially CXCL10/interferon (IFN)-gamma-inducible protein 10 (IP-10), a chemokine to attract CXCR3+ T helper 1-type CD4+ T cells, has not been investigated thoroughly in the pathogenesis of pancreatitis. B6 mice were inoculated intraperitoneally with LP-BM5 and then injected every week with either an antibody against IP-10 or a control antibody. Eight weeks after infection, we analyzed the effect of IP-10 neutralization. Anti-IP-10 antibody treatment did not change the generalized lymphadenopathy and hepatosplenomegaly of mice with MAIDS. The treatment significantly reduced the number of IP-10- and CXCR3-positive cells in the mesenteric lymph nodes (mLNs) but not the phenotypes and gross numbers of cells. In contrast, IP-10 neutralization reduced the number of mononuclear cells infiltrating into the pancreas. Anti-IP-10 antibody treatment did not change the numbers of IFN-gamma+ and IL10+ cells in the mLN but significantly reduced their numbers, especially IFN-gamma+ and IL-10+ CD4+ T cells and IFN-gamma+ Mac-1+ cells, in the pancreas. IP-10 neutralization ameliorated the pancreatic lesions of mice with MAIDS probably by blocking the cellular infiltration of CD4+ T cells and IFN-gamma+ Mac-1+ cells into the pancreas at least at 8 wk after infection, suggesting that IP-10 and these cells might play a key role in the development of chronic autoimmune pancreatitis.
Kawauchi
Yusuke
Y
Department of Gastroenterology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
Suzuki
Kenji
K
Watanabe
Shiro
S
Yamagiwa
Satoshi
S
Yoneyama
Hiroyuki
H
Han
Gi Dong
GD
Palaniyandi
Suresh S
SS
Veeraveedu
Punniyakoti T
PT
Watanabe
Kenichi
K
Kawachi
Hiroshi
H
Okada
Yoshiaki
Y
Shimizu
Fujio
F
Asakura
Hitoshi
H
Aoyagi
Yutaka
Y
Narumi
Shosaku
S
D000818:Animals; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D007155:Immunologic Factors / Q000276:immunology*; D051379:Mice; D016183:Murine Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000276:immunology*; D010195:Pancreatitis / Q000209:etiology* / Q000276:immunology*; D012192:Retroviridae Infections / Q000150:complications / Q000276:immunology
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C485433:Cxcl10 protein, mouse; D007155:Immunologic Factors