Partial purification of the cholestatic factor derived from the lymphocytes of tuberculin-sensitized guinea pigs

Abstract

When lymph node lymphocytes from the tuberculin-sensitized guinea pigs were stimulated in vitro with PPD (purified protein derivatives) and the culture fluid was injected into the mesenteric vein of rats, a marked reduction of bile flow was observed. These culture supernatants contained cholestatic activity were fractionated by gel filtration using a Sephadex G-75 column followed by DEAE-cellulose column chromatography. Both the cholestatic activity and the macrophage migration inhibitory factor (MIF) activity were detected predominantly in the fourth fraction of gel filtration. By further fractionation using a DEAE-cellulose column chromatography, the cholestatic activity was separated into two fractions; one of them was shown to have both cholestatic activity and MIF activity, but the other did not have any detectable MIF activity. These results suggest that the cholestatic factor may be different at least partially from the MIF.

Studies of the influence of immunological and serological factors from patients with cholestasis due to alcoholic or viral hepatitis on biliary function in the rat

“…The present study was undertaken to test this hypothesis by evaluating the influence on rat bile flow of supernatants of sensitized cultured lymphocytes from patients with cholestatic viral or alcoholic hepatitis. An animal model with tuberculin-sensitized guinea pigs [2] was used to investigate possible mechanisms by which these supernatants of cultured lymphocytes could interfere with bile flow and could contribute to the development of cholestasis.…”

Allergic Hepatitis in Guinea Pigs Induced by 2,4,6-Trinitrophenyl Liver Protein Conjugate

“…Mizoguchi and co-workers reported the pos sible involvement of macrophage-mediated hepatocy totoxicity in the pathogenesis of liver injuries [24,25] and the provocation of liver injury by the presence of lipopolysaccharide (LPS) in hepatomononuclcocytosis by treatment with CFA and P. acnes [12]. We are now observing the exacerbation of liver injury to le thal levels by combination treatment with LPS and TNP-hepatocytes to TNP-LPl-sensitizcd guinea pigs [in preparation], Mizoguchi and co-workers observed the cholestatic factor (CF, a kind of DTH lymphokine [26]) in the culture supernatant of PBL from patients with druginduced allergic hepatitis of intrahcpatic cholestasis [27], In the present study, we observed neither intrahepatic cholestasis nor a high level of serum T. bil in spite of the development of DTH inside the liver. This discrepancy may have been caused by the differences in experimental conditions: (1) differences in species used; (2) differences in the type of cells that infil trated the inflammation sites; (3) possible contamina tion of LPS, and (4) participation of humoral immuni ty.…”