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Mast Cell Density, Hepatic Stellate Cell Activation and TGF-β1 Transcripts in the Aging Sprague-Dawley Rat During Early Acute Liver Injury

Direzione Scientifica, Istituto Clinico Humanitas, Rozzano, Milan, fabio.grizzi{at}humanitas.it, Fondazione "Michele Rodriguez," Istituto Scientifico per le Misure Quantitative in Medicina, Milan, Italy

B. Franceschini

Direzione Scientifica, Istituto Clinico Humanitas, Rozzano, Milan, Fondazione "Michele Rodriguez," Istituto Scientifico per le Misure Quantitative in Medicina, Milan, Italy

N. Gagliano

Dipartimento di Anatomia Umana, University of Milan, Italy

C. Moscheni

Dipartimento di Anatomia Umana, University of Milan, Italy

G. Annoni

Dipartimento di Medicina Interna, Ospedale Maggiore, IRCCS, Milan, Italy

C. Vergani

Dipartimento di Medicina Interna, Ospedale Maggiore, IRCCS, Milan, Italy

P.L. Hermonat

Division of Obstetrics and Gynecology, University of Arkansas Medical Sciences, Little Rock, Arkansas, USA

M. Chiriva-Internati

Texas Tech University Health Science Center, and Don and Sybil Harrington Cancer Center, Amarillo, Texas, USA

N. Dioguardi

Direzione Scientifica, Istituto Clinico Humanitas, Rozzano, Milan, Fondazione "Michele Rodriguez," Istituto Scientifico per le Misure Quantitative in Medicina, Milan, Italy

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 (CCl4) 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.

Key Words: Liver • mast cells • hepatic stellate cells • myofibroblasts • CCl4 intoxication • inflammation • collagen synthesis • transforming-growth factor-b1.

Toxicologic Pathology, Vol. 31, No. 2, 173-178 (2003)
DOI: 10.1080/01926230390183643


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