Sublobular veins as the main site of lymphocyte adhesion/transmigration and adhesion molecule expression in the porto-sinusoidal-hepatic venous system during concanavalin A-induced hepatitis in mice

Abstract

Lymphocyte infiltration is a manifest feature of hepatitis. To reveal the main site and mechanism of lymphocyte adhesion/extravasation in the hepatic vasculature during inflammation, we morphometrically and histologically analyzed these events in relation to adhesion molecule expression using a murine model of T-cell mediated hepatitis induced by concanavalin A (Con A). Although lymphocyte adhesion was restricted to the sinusoids in untreated mice, it increased in all the segments of porto-sinusoidal-hepatic venous system 8 hours after Con A injection; the number of adhering lymphocytes per unit vascular circumference was the largest in the sublobular veins, relatively large in the central veins and small hepatic veins, and relatively small in the sinusoids and negligible in the portal veins. At 20 hours, extravascular lymphocytes showed similar distribution to lymphocyte adhesion at 8 hours except in the portal veins, around which they were possibly accumulated by the translocation of extrasinusoidal lymphocytes. E-selectin and vascular cell adhesion molecule-1 (VCAM-1) were transiently expressed at 4 to 6 hours, whereas P-selectin and intercellular adhesion molecule-1 were not changed between 0 and 48 hours. In particular, E-selectin expression coincided with that of lymphocyte adhesion in distribution.

Peribronchiolar accumulation of dendritic cells and their close association with CD4+ T cells in the murine lung hypersensitivity

“…This interpretation was confirmed by the present finding of lymphocyte extravasation in the capillaries of the peribronchiolar interstitium. Lymphocytes adhered to the endothelium and underwent diapedesis as previously observed in the hepatic venules (Morikawa et al, 2000). After emigration, lymphocytes made a close apposition to DCs.…”

Massive liver necrosis after provocation of imbalance between Th1 and Th2 immune reactions in osteopontin transgenic mice

“…It is reported that the concentrations of IFN-γ and TNF-α were upregulated in both C57BL/6 and BALB/c mice after concanavalin-A administration, 26,27 and pretreatment with neutral antibody against IFN-γ attenuated plasma ALT activity almost completely in C57BL/6 mice, 26 while anti-TNF-α antibody was more effective than anti-IFN-γ antibody in BALB/c mice. 27 The significance of TNF-α in the development of concanavalin-Ainduced liver injury may differ depending on the strains of mice. It seems likely that IFN-γ, but not TNF-α, may play a crucial role in the development of liver injury in the transgenic mice established from C57BL/6 mice.…”

TNF-α-Induced Expression of Adhesion Molecules in the Liver Is Under the Control of TNFR1—Relevance for Concanavalin A-Induced Hepatitis

“…n ϭ 4 per group; ‫,ء‬ p Յ 0.05 vs the corresponding control mAb pretreated, Con A-injected group. mAb (39) or anti-ICAM-1 mAb but not anti-VCAM-1 mAb (18). These controversial findings might have been due to different pretreatment regiments, e.g., Ab pretreatment 24 and 48 h before Con A injection, which might have depleted intrahepatic lymphocytes critical for the development of liver injury.…”