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The role of CXCR3 in the induction of primary biliary cirrhosis.

Zhang W, Fei Y, Gao J, Liu B, Zhang F - Clin. Dev. Immunol. (2011)

Bottom Line: PBC model was confirmed by liver function, serum autoantibodies and liver biopsy.CXCR3 might contribute to the development of PBC in murine model.Knockout of CXCR3 might delay and alleviate the PBC disease progression, but could not entirely block the disease development.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.

ABSTRACT

Objective: Investigate whether CXCR3 and its ligands were involved in the pathogenesis of primary biliary cirrhosis (PBC) in an autoimmune cholangitis animal model.

Methods: Female C57BL/6 mice were injected with 5 mg/kg of poly I:C intraperitoneally twice a week for 24 weeks. PBC model was confirmed by liver function, serum autoantibodies and liver biopsy. Lymphocytes subsets in liver and spleen and CXCL10 serum level were tested by flow cytometry and ELISA. Liver specimens were collected to evaluate the differences in pathology between WT and CXCR3(-/-) mice.

Results: Antimitochondrial antibody was detected in all PBC model. Numbers of infiltrates were detected in the portal areas 8 weeks after poly I:C injection, which progressed up to 24 weeks. Compared to control mice, CXCL10 serum level increased in PBC mice and the proportion of CXCR3(+) cells increased in the intrahepatic infiltrates of PBC mice, chiefly on CD8(+) cells, whereas the expression of CXCR3 on CD3(+) and CD8(+) splenocytes decreased in PBC model. Compared with WT mice, CXCR3(-/-) mice developed delayed and milder progression of cellular inflammation.

Conclusions: CXCR3 might contribute to the development of PBC in murine model. Knockout of CXCR3 might delay and alleviate the PBC disease progression, but could not entirely block the disease development.

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Related in: MedlinePlus

Serial observation of mononuclear cells infiltration in the liver tissue. Female C57BL/6 mice were injected with 5 mg/kg of poly I:C twice a week for 24 consecutive weeks. Liver specimens were collected at 8 weeks (a–d), 16 weeks (e–h), and 24 weeks (i–l) after the start of poly I:C injection and were underwent HE staining. Different degrees of lymphocytic infiltration surrounding the small bile ducts were detected within the portal tracts. A representative staining pattern from each period is shown as following: (a, b) Week 8 of WT PBC mice. (c, d) Week 8 of CXCR3−/− PBC mice. (e, f) Week 16 of WT PBC mice. (g, h) Week 16 of CXCR3−/− PBC mice. (I, k) Week 24 of WT PBC mice. (j, l) Week 24 of CXCR3−/− PBC mice. Note: Magnification: (a, c, e, g, i, j) × 5; (b, d, f, h, k, l) × 20, × 40.
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fig5: Serial observation of mononuclear cells infiltration in the liver tissue. Female C57BL/6 mice were injected with 5 mg/kg of poly I:C twice a week for 24 consecutive weeks. Liver specimens were collected at 8 weeks (a–d), 16 weeks (e–h), and 24 weeks (i–l) after the start of poly I:C injection and were underwent HE staining. Different degrees of lymphocytic infiltration surrounding the small bile ducts were detected within the portal tracts. A representative staining pattern from each period is shown as following: (a, b) Week 8 of WT PBC mice. (c, d) Week 8 of CXCR3−/− PBC mice. (e, f) Week 16 of WT PBC mice. (g, h) Week 16 of CXCR3−/− PBC mice. (I, k) Week 24 of WT PBC mice. (j, l) Week 24 of CXCR3−/− PBC mice. Note: Magnification: (a, c, e, g, i, j) × 5; (b, d, f, h, k, l) × 20, × 40.

Mentions: After injection with 5 mg/kg of poly I:C, different degrees of lymphocytic infiltration surrounding the small bile ducts were detected within the portal tracts (HE staining) in WT C57BL/6 mice. Representative staining patterns of mononuclear cell infiltration in the liver tissues are shown in Figure 5. Mononuclear cell infiltration in the liver tissues was detected at 8 weeks after poly I:C injection Figures 5(a), and 5(b) and progressively increased with time. A representative staining pattern of portal areas at 16 weeks after the start of poly I:C injection is shown in Figures 5(e), 5(f), which reveals irregular nuclear arrangement of interlobular bile ducts, distorted lumen and detachment of cells, as well as infiltrating cells accumulated around the damaged bile duct, resembling chronic nonsuppurative destructive cholangitis as seen in PBC. In 24-week period, the interlobular bile ducts were lost, bileplugs were evident in the livers of WT PBC mice, and granulomas formation was detected as well (Figures 5(i), and 5(k)). Furthermore there was a mild interface hepatitis (piecemeal necrosis), and, in a few instances, infiltrates were evident adjacent to the central vein.


The role of CXCR3 in the induction of primary biliary cirrhosis.

Zhang W, Fei Y, Gao J, Liu B, Zhang F - Clin. Dev. Immunol. (2011)

Serial observation of mononuclear cells infiltration in the liver tissue. Female C57BL/6 mice were injected with 5 mg/kg of poly I:C twice a week for 24 consecutive weeks. Liver specimens were collected at 8 weeks (a–d), 16 weeks (e–h), and 24 weeks (i–l) after the start of poly I:C injection and were underwent HE staining. Different degrees of lymphocytic infiltration surrounding the small bile ducts were detected within the portal tracts. A representative staining pattern from each period is shown as following: (a, b) Week 8 of WT PBC mice. (c, d) Week 8 of CXCR3−/− PBC mice. (e, f) Week 16 of WT PBC mice. (g, h) Week 16 of CXCR3−/− PBC mice. (I, k) Week 24 of WT PBC mice. (j, l) Week 24 of CXCR3−/− PBC mice. Note: Magnification: (a, c, e, g, i, j) × 5; (b, d, f, h, k, l) × 20, × 40.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3102447&req=5

fig5: Serial observation of mononuclear cells infiltration in the liver tissue. Female C57BL/6 mice were injected with 5 mg/kg of poly I:C twice a week for 24 consecutive weeks. Liver specimens were collected at 8 weeks (a–d), 16 weeks (e–h), and 24 weeks (i–l) after the start of poly I:C injection and were underwent HE staining. Different degrees of lymphocytic infiltration surrounding the small bile ducts were detected within the portal tracts. A representative staining pattern from each period is shown as following: (a, b) Week 8 of WT PBC mice. (c, d) Week 8 of CXCR3−/− PBC mice. (e, f) Week 16 of WT PBC mice. (g, h) Week 16 of CXCR3−/− PBC mice. (I, k) Week 24 of WT PBC mice. (j, l) Week 24 of CXCR3−/− PBC mice. Note: Magnification: (a, c, e, g, i, j) × 5; (b, d, f, h, k, l) × 20, × 40.
Mentions: After injection with 5 mg/kg of poly I:C, different degrees of lymphocytic infiltration surrounding the small bile ducts were detected within the portal tracts (HE staining) in WT C57BL/6 mice. Representative staining patterns of mononuclear cell infiltration in the liver tissues are shown in Figure 5. Mononuclear cell infiltration in the liver tissues was detected at 8 weeks after poly I:C injection Figures 5(a), and 5(b) and progressively increased with time. A representative staining pattern of portal areas at 16 weeks after the start of poly I:C injection is shown in Figures 5(e), 5(f), which reveals irregular nuclear arrangement of interlobular bile ducts, distorted lumen and detachment of cells, as well as infiltrating cells accumulated around the damaged bile duct, resembling chronic nonsuppurative destructive cholangitis as seen in PBC. In 24-week period, the interlobular bile ducts were lost, bileplugs were evident in the livers of WT PBC mice, and granulomas formation was detected as well (Figures 5(i), and 5(k)). Furthermore there was a mild interface hepatitis (piecemeal necrosis), and, in a few instances, infiltrates were evident adjacent to the central vein.

Bottom Line: PBC model was confirmed by liver function, serum autoantibodies and liver biopsy.CXCR3 might contribute to the development of PBC in murine model.Knockout of CXCR3 might delay and alleviate the PBC disease progression, but could not entirely block the disease development.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.

ABSTRACT

Objective: Investigate whether CXCR3 and its ligands were involved in the pathogenesis of primary biliary cirrhosis (PBC) in an autoimmune cholangitis animal model.

Methods: Female C57BL/6 mice were injected with 5 mg/kg of poly I:C intraperitoneally twice a week for 24 weeks. PBC model was confirmed by liver function, serum autoantibodies and liver biopsy. Lymphocytes subsets in liver and spleen and CXCL10 serum level were tested by flow cytometry and ELISA. Liver specimens were collected to evaluate the differences in pathology between WT and CXCR3(-/-) mice.

Results: Antimitochondrial antibody was detected in all PBC model. Numbers of infiltrates were detected in the portal areas 8 weeks after poly I:C injection, which progressed up to 24 weeks. Compared to control mice, CXCL10 serum level increased in PBC mice and the proportion of CXCR3(+) cells increased in the intrahepatic infiltrates of PBC mice, chiefly on CD8(+) cells, whereas the expression of CXCR3 on CD3(+) and CD8(+) splenocytes decreased in PBC model. Compared with WT mice, CXCR3(-/-) mice developed delayed and milder progression of cellular inflammation.

Conclusions: CXCR3 might contribute to the development of PBC in murine model. Knockout of CXCR3 might delay and alleviate the PBC disease progression, but could not entirely block the disease development.

Show MeSH
Related in: MedlinePlus