FIG. 2.

Glutathione depletion differentially inhibits hepatic inflammatory responses in mice challenged with 5 × 10⁷ E. coli bacteria. All injections were by the i.p. route. Immunohistology was used to detect the expression of specific proteins in the livers of the following groups of mice. (A) HSP-32 staining in mice 5 h after the injection of DEM (see Fig. 1A). Note the expression of HSP-32 by Kupffer cells (solid arrow), hepatocytes (open arrow) and hepatic sinusoidal endothelial cells (arrowhead). (B) TNF-α staining in Kupffer cells (solid arrow) 1.5 h after vehicle-treated mice were challenged with E. coli bacteria. (C) TNF-α staining 1.5 h after DEM-treated mice were challenged with E. coli. Note the absence of TNF-α expression. (D) iNOS staining of Kupffer cells (solid arrow), hepatocytes (open arrow), and hepatic sinusoidal endothelial cells (arrowhead) 6 h after challenging vehicle-treated mice with E. coli. (E) iNOS staining in DEM-treated mice challenged with E. coli. (F) ICAM-1 staining of Kupffer cells (solid arrow) and endothelial cells (arrowhead) 6 h after challenge of the vehicle control group with E. coli. (G) ICAM-1 staining in DEM-treated, E. coli-challenged mice. (H) iNOS staining in DEM-treated mice that were challenged with 4 mg of LPS/kg of body weight showing positive Kupffer cells (solid arrow) and sinusoidal endothelial cells (arrowhead). (I) iNOS staining in DEM-treated mice that were challenged with 4 mg LPS plus 80 μg of recombinant IFN-γ per kg of body weight. Note the staining of all three hepatic cell types, which is similar to that seen in infected mice (panel E above). (J) ICAM-1 staining in DEM-treated mice that were challenged with LPS. (K) ICAM-1 staining in DEM-treated mice challenged with LPS and recombinant IFN-γ. The intense staining is similar that seen in infected mice (panel G above). (L) ICAM-1 staining of Kupffer cells (solid arrow) and endothelial cells (arrowhead) in wild-type BALB/c mice infected with E. coli. (M) ICAM-1 staining in wild-type BALB/c mice treated with DEM and then infected with E. coli. Note the similar staining pattern as in panel L. (N) ICAM-1 staining in IFN-γ-null mice treated with DEM and challenged with E. coli. Note the presence of sinusoidal leukocytes expressing ICAM-1 (circled). (O) F4/80 staining of Kupffer cells (solid arrow) in IFN-γ-null mice treated with DEM and challenged with E. coli. Sinusoidal leukocytes (circled) are negative. Original magnification, ×250.