TY - JOUR
T1 - Mast cell density, hepatic stellate cell activation and TGF-β1 transcripts in the aging Sprague-Dawley rat during early acute liver injury
AU - Grizzi, F.
AU - Franceschini, B.
AU - Gagliano, N.
AU - Moscheni, C.
AU - Annoni, G.
AU - Vergani, C.
AU - Hermonat, P. L.
AU - Chiriva-Internati, M.
AU - Dioguardi, N.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2003/3
Y1 - 2003/3
N2 - Mast cells (MCs) have been indicated as a source of various inflammatory cytokines, chemokines and growth factors. This study evaluates liver tissue MC density as a quantitative marker of acute liver inflammation in 2- and 19-month old rats treated with carbon tetrachloride (CC14) to assess the relationships between MC density, hepatocellular damage, mRNA encoding TGF-β1, hepatic stellate cell (HSC) activation and collagen levels. Consecutive histological sections from each age group were stained with toluidine blue to identify granulated MCs, Direct Red 80 to recognize collagen matrix, and by immunohistochemistry to identify activated hepatic stellate cells (HSCs), which were subsequently counted by means of a computer-aided image analysis. Histology showed hepatocellular necrosis with inflammatory cell infiltration and collagen matrix deposition. Two and 24 hours after intoxication, MC density had considerably increased in the younger rats, but less in those aged 19 months. Although the untreated older rats had a larger area occupied by activated HSCs than the untreated younger rats, the increase in the number of HSCs was greater in the younger rats both two and 24 hours after intoxication. The greater MC density in younger rats suggests that older rats have a reduced immune response or recruit fewer MCs. The activated HSCs and TGF-β1 transcripts did not increase significantly during the study period, thus indicating that these are later events in chemically induced hepatic toxicity. In conclusion, MC density may be an index of acute liver inflammation after CCl4 intoxication.
AB - Mast cells (MCs) have been indicated as a source of various inflammatory cytokines, chemokines and growth factors. This study evaluates liver tissue MC density as a quantitative marker of acute liver inflammation in 2- and 19-month old rats treated with carbon tetrachloride (CC14) to assess the relationships between MC density, hepatocellular damage, mRNA encoding TGF-β1, hepatic stellate cell (HSC) activation and collagen levels. Consecutive histological sections from each age group were stained with toluidine blue to identify granulated MCs, Direct Red 80 to recognize collagen matrix, and by immunohistochemistry to identify activated hepatic stellate cells (HSCs), which were subsequently counted by means of a computer-aided image analysis. Histology showed hepatocellular necrosis with inflammatory cell infiltration and collagen matrix deposition. Two and 24 hours after intoxication, MC density had considerably increased in the younger rats, but less in those aged 19 months. Although the untreated older rats had a larger area occupied by activated HSCs than the untreated younger rats, the increase in the number of HSCs was greater in the younger rats both two and 24 hours after intoxication. The greater MC density in younger rats suggests that older rats have a reduced immune response or recruit fewer MCs. The activated HSCs and TGF-β1 transcripts did not increase significantly during the study period, thus indicating that these are later events in chemically induced hepatic toxicity. In conclusion, MC density may be an index of acute liver inflammation after CCl4 intoxication.
KW - CCl intoxication
KW - Collagen synthesis
KW - Hepatic stellate cells
KW - Inflammation
KW - Liver
KW - Mast cells
KW - Myofibroblasts
KW - Transforming-growth factor-b
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U2 - 10.1080/01926230309803
DO - 10.1080/01926230309803
M3 - Article
C2 - 12696576
AN - SCOPUS:0037348635
SN - 0192-6233
VL - 31
SP - 173
EP - 178
JO - Toxicologic pathology
JF - Toxicologic pathology
IS - 2
ER -