References
Query Results -- Details
MGI Accession ID: MGI:3778865
J Number: J:133582
Other Accession IDs:
Title: Immunomodulatory effects of plasminogen activators on hepatic fibrogenesis.
Authors: Higazi AA; El-Haj M; Melhem A; Horani A; Pappo O; Alvarez CE; Muhanna N; Friedman SL; Safadi R
Journal: Clin Exp Immunol
Volume: 152
Issue: 1
Date: 2008 Apr
Year: 2008
Pages: 163-73
Review Status: Peer Reviewed
Abstract:
Tissue-type plasminogen activators (tPA) and urokinase-type plasminogen activators (uPA) are involved in liver repair. We examined the potential immunomodulatory actions of uPA, tPA and uPA-receptor (uPAR) in carbon-tetrachloride-induced hepatic fibrosis in wild-type (WT), tPA-/-, uPA-/- and uPAR-/- mice. Carbon-tetrachloride treatment increased fibrosis in four groups but significantly less in three knock-out models. Serum cytokines and intrahepatic T cells elevated significantly following fibrosis process in WT animals but not in the knock-out groups. In culture, uPA increased lymphocyte proliferation significantly in WT and uPA-/- but not uPAR-/- animals. Following uPA exposure in vivo, there was CD8 predominance. To isolate uPA's effect on lymphocytes, WT mice were irradiated sublethally and then reconstituted with WT or uPA-/- lymphocytes. In these animals fibrosis was decreased and T cells were reduced in the uPA-/- recipients. Based on these data we postulate that plasminogen activators affect fibrosis in part by liver-specific activation of CD8 subsets that govern the fibrogenic activity of hepatic stellate cells.
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