Interleukin-1 2-Induced Adhesion Molecule Expression inMurine Liver

Systemically administered interleukin (IL)-12 causes liver inflammation inmicecharcterized byKupffer cell proliferation andhypertrophy, hepatocyte necrosis, andmultifocal accumulations ofleukocytes inthehepatic parenchyma andaroundportal tracts andcentral veins. We haveusedbothm histochemical stainingandradiolabeled antibody quantitation toexamine adhesion molecule expression Inthelivers ofmice doseddaily withmurineHL12. Cells Infiltnglivers of IL-12-treated micewereprimarily mononudearleukocytes expressing LFA-1, VIA-4, MAC-1,andCD18adhesionmolecules butlitde Iselectln. Kupffer cells constitutively expressed LFA-1andsmaller amountsofMAC-1, andhighlevels ofICAM-1wereconstitutively expressed byliver sinusoidal lining cells, portal tract, andcentral veinendothelia. WithIL12treatment, existing ICAM-1 expression wasup-regulated anddenovoexpression occurred along bile ductepithelia. VCAM-1levels were dramatically increased, withinduced expression occurringalongportal tract andcentral veinendothelia and scattedbile ductepithelial cells andinaggretions of cells inperivascular areasandtheliver parenchyma. Although constitutive expression ofE-andP-selectin wasn ble,I1-12 induced amoderate rise inE-selectinlevels. These increases inadhesion molecule expressionmayhaveimplications forthetherapeutic useof 11-12, especially inpatients withliver disease orautoimmuneconditions whereaugmented adhesion moleculeexpression maybecritical todisease pathogenesis. (AmjPathol 1998152:457-468)