Suppression of hepatic lesions in a murine graft-versus-host reaction by antibodies against adhesion molecules - PubMed (original) (raw)
Suppression of hepatic lesions in a murine graft-versus-host reaction by antibodies against adhesion molecules
S Itoh et al. J Hepatol. 2000 Apr.
Abstract
Background/aims: The injection of parental CD4+ T cells into major histocompatibility complex (MHC) class II disparate F1 hybrid mice induced an autoimmune graft-versus-host reaction (GVHR) which is analogous to autoimmune liver diseases. The interaction of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) and very late antigen-4 (VLA-4) has been known to be profoundly involved in the trafficking of lymphocytes into the inflammatory tissues. The aim of this study was to clarify the role of VLA4 or VCAM-1 in the development of GVHR-induced hepatic lesions in our model.
Methods: B6 T spleen cells were injected into (B6.C-H-2bm12xB6) F1 mice intravenously. Anti-VLA-4 mAbs and/or anti-VCAM-1 mAbs were injected intraperitoneally at a dose of 2.5 mg/kg of each mAbs per body weight of mouse. We examined the changes in GVHR-induced hepatic lesions, serum levels of antimitochondrial antibodies (AMA) and cytokine mRNA expressions of liver-infiltrating lymphocytes using H.E. and immunohistochemical staining, enzyme-linked immunosorbent assay (ELISA), and reverse transcription-polymerase chain reaction (RT-PCR), respectively.
Results: Hepatic lesions of anti-VLA-4 mAbs-treated mice were inhibited compared with those of GVHR mice. However, the administration of mAbs did not interfere with the induction of splenomegaly, the invasion of CD4+, CD8+, B220+, or Mac-1+ cells around bile ducts, nor the production of AMA. Liver-infiltrating CD4+ T cells obtained from these treated mice did not alter the expression of T helper (Th)1 and Th2 cytokine mRNA.
Conclusion: The results suggest that treatment with antibodies against these adhesion molecules could inhibit the infiltration of lymphocytes without affecting the Th1/Th2 balance. The blockade of VLA-4-mediated cell infiltration into the liver in this model may have a possible novel therapeutic role of VLA-4 mAbs.
Similar articles
- Novel murine autoimmune-mediated liver disease model induced by graft-versus-host reaction and concanavalin A.
Unno R, Matsuzaki Y, Itoh S, Doy M, Shoda J, Tanaka N. Unno R, et al. J Gastroenterol Hepatol. 2001 Oct;16(10):1149-57. doi: 10.1046/j.1440-1746.2001.02580.x. J Gastroenterol Hepatol. 2001. PMID: 11686843 - Cytokine profile of liver-infiltrating CD4+ T cells separated from murine primary biliary cirrhosis-like hepatic lesions induced by graft-versus-host reaction.
Itoh S, Matsuzaki Y, Kimura T, Ikegami T, Shoda J, Fujiwara M, Tanaka N. Itoh S, et al. J Gastroenterol Hepatol. 2000 Apr;15(4):443-51. doi: 10.1046/j.1440-1746.2000.02068.x. J Gastroenterol Hepatol. 2000. PMID: 10824891 - Differential Th1 and Th2 cell regulation of murine cardiac allograft acceptance by blocking cell adhesion of ICAM-1/LFA-1 and VCAM-1/VLA-4.
Suzuki J, Isobe M, Izawa A, Takahashi W, Yamazaki S, Okubo Y, Amano J, Sekiguchi M. Suzuki J, et al. Transpl Immunol. 1999 Mar;7(1):65-72. doi: 10.1016/s0966-3274(99)80021-5. Transpl Immunol. 1999. PMID: 10375080 - Mechanisms of stem-/progenitor-cell mobilization: the anti-VLA-4 paradigm.
Papayannopoulou T. Papayannopoulou T. Semin Hematol. 2000 Jan;37(1 Suppl 2):11-8. doi: 10.1016/s0037-1963(00)90084-2. Semin Hematol. 2000. PMID: 10718154 Review. - Immunosuppression by blocking alpha 4-integrins/VCAM-1 adhesion.
Isobe M, Hori J, Suzuki J. Isobe M, et al. Curr Top Microbiol Immunol. 1998;231:85-98. doi: 10.1007/978-3-642-71987-5_6. Curr Top Microbiol Immunol. 1998. PMID: 9479862 Review. No abstract available.
Cited by
- Gas6 deficiency in recipient mice of allogeneic transplantation alleviates hepatic graft-versus-host disease.
Burnier L, Saller F, Kadi L, Brisset AC, Sugamele R, Baudino L, Bono F, Herbert JM, Carmeliet P, Schapira M, Izui S, Angelillo-Scherrer A. Burnier L, et al. Blood. 2010 Apr 22;115(16):3390-7. doi: 10.1182/blood-2009-02-206920. Epub 2010 Feb 4. Blood. 2010. PMID: 20139094 Free PMC article. - Therapeutic anti-integrin (alpha4 and alphaL) monoclonal antibodies: two-edged swords?
González-Amaro R, Mittelbrunn M, Sánchez-Madrid F. González-Amaro R, et al. Immunology. 2005 Nov;116(3):289-96. doi: 10.1111/j.1365-2567.2005.02225.x. Immunology. 2005. PMID: 16236118 Free PMC article. Review. - Leukocyte migration and graft-versus-host disease.
Wysocki CA, Panoskaltsis-Mortari A, Blazar BR, Serody JS. Wysocki CA, et al. Blood. 2005 Jun 1;105(11):4191-9. doi: 10.1182/blood-2004-12-4726. Epub 2005 Feb 8. Blood. 2005. PMID: 15701715 Free PMC article. Review. - Novel expression of vascular cell adhesion molecule-1 (CD106) by squamous epithelium in experimental acute graft-versus-host disease.
Kim JC, Whitaker-Menezes D, Deguchi M, Adair BS, Korngold R, Murphy GF. Kim JC, et al. Am J Pathol. 2002 Sep;161(3):763-70. doi: 10.1016/S0002-9440(10)64235-6. Am J Pathol. 2002. PMID: 12213703 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous