Spontaneous and antibody-dependent cellular immune reactions to ethanol-altered hepatoma cells

— Spontaneous cell-mediated cytotoxicity (SCMC), antibody-dependent cellular cytotoxicity (ADCC) and proliferative lymphocyte stimulation in alcoholic liver disease (ALD) were investigated. Peripheral blood lymphocytes (PBL) from eight patients with advanced ALD and nine normal controls were tested against hepatoma cells (PLC/PRF/5) as targets. Target cells were grown in either normal culture medium or medium supplemented with 1 and 5% ethanol, respectively, for 24 to 48 h. Ethanol-exposed hepatoma cells exhibited profound and characteristic morphological alterations. Ethanol preincubation, however, proved to be without effect on immune reactions. Provided that hepatoma cells are an appropr…

Analysis of liver-specific protein LSP using murine monoclonal antibodies.

. We describe twenty murine monoclonal antibodies directed against different antigenic determinants of human and rabbit liver-specific protein LSP. Among them, nine were directed against liver-specific epitopes as judged from immunohistological studies. Immunoelectronmicroscopy revealed that seven of these monoclonals recognized membrane determinants differing in staining of distinct areas of the hepatocellular surface. Eleven antibodies were directed against intracellular structures. Western blot analysis showed that the epitopes detected were displayed on either single or multiple protein bands with apparent molecular weights between 24 000 and 60 000. Further differences were observed wi…

Impaired cellular immune responses in chronic renal failure: Evidence for a T cell defect

Impaired cellular immune responses in chronic renal failure: Evidence for a T cell defect. Cellular immune responses in vitro were studied in 24 patients on chronic hemodialysis and 16 healthy volunteers with normal kidney function. Patients on maintenance hemodialysis had lymphopenia with diminished numbers of both T4 + and T8 + T-lymphocytes. The T4/T8 ratios were within the normal range. Peripheral blood lymphocytes (PBL) showed a diminished proliferative response upon stimulation with concanavalin A, phytohemagglutinin and poke weed mitogen. When cell surface antigens were used for stimulation (mixed lymphocyte culture) uremic lymphocytes also showed a lower proliferation rate. Although…

Liver cell damage caused by monoclonal antibody against an organ-specific membrane antigen in vivo and in vitro

Summary Monoclonal antibodies have been raised against different antigenic determinants of normal rabbit hepatocytes. One antibody (2D3) recognized a liver-specific 43 kDa protein displayed exclusively on the basolateral portion of the hepatocellular membrane. Purified monoclonal antibodies were injected intravenously into rabits. Following the injection of antibody 2D3, a dose-dependent increase of liver enzyme activities in sera was observed. Within 8 h, marked morphological alterations of the hepatocytes, including multiple cell necroses, could be demonstrated by light and electron microscopy. When isolated vital rabbit hepatocytes in culture were used as targets, cytotoxic effects of th…

Cellular cytotoxicity against the human hepatoma cell line PLC/PRF/5 in patients with hepatitis B virus-induced chronic active hepatitis (CAH) and non-A, non-B (NANB) CAH

Immune Reactions in Liver Diseases

Chronic hepatitis is a heterogeneous syndrome with different underlying etiologies. Viruses (hepatitis B virus, non-A, non-B viruses), drugs and even alcohol are regarded as etiological agents. A further subgroup is autoimmune-type chronic hepatitis in which an immunogenetic predisposition is of major importance. Primary biliary cirrhosis has to be separated from these subgroups of chronic hepatitis.

Treatment of hepatitis B surface antigen (HBsAg)-positive chronic hepatitis with recombinant leucocyte α-A interferon

A total of 32 individuals with HBsAg-positive and anti-delta-negative chronic hepatitis were treated with recombinant alpha-A interferon in phase I and phase II studies. In 5/32 patients HBsAg could be eliminated and in 19/32 individuals HBeAg became negative including all those who also eliminated HBsAg. Side-effects were tolerable in most patients and were readily reversible upon discontinuation of interferon therapy. In conclusion, treatment of HBsAg-positive chronic hepatitis with interferon seems to be a promising therapeutic approach. Future studies will have to establish the optimal dose, duration of treatment and factors predicting a favourable outcome of the treatment.

Immunoelectron microscopic observations on the inflammatory infiltrates and HLA antigens in hepatitis B and non-A, non-B.

The present knowledge of the inflammatory reaction occurring in situ during hepatitis B favors a T cell-dependent MHC-restricted immune response. However, the reports in the literature are primarily based on the application of monoclonal antibodies directed at different lymphocyte subsets which discern only lymphocytic phenotypes and do not reflect the actual situation adequately. Therefore, we investigated the liver biopsies of patients with hepatitis B (28 patients) and non-A, non-B (21 patients) by immunoelectron microscopy with monoclonal antibodies directed at lymphocyte subtypes (pan-B, pan-T, T8, T4 and NKH1) and at activation epitopes (IL-2 receptor, TA1 and T11/3) as well, in order…

Cellular cytotoxicity against autologous hepatocytes in alcoholic liver disease.

We tested lymphocyte cytotoxicity against autologous hepatocytes in patients with alcoholic liver disease (ALD). The following cytotoxicity values were found (mean +/- SEM): alcohol-induced steatosis with or without fibrosis 16.5 +/- 2% (n = 29), alcoholic cirrhosis 28 +/- 4% (n = 13), controls with normal liver histology or minimal changes 6 +/- 2% (n = 11). The differences were statistically significant (both forms of ALD versus controls p less than 0.005). T-cell as well as non-T-cell-enriched lymphocyte fractions showed increased cytotoxicity in ALD. We did not observe a correlation between cellular cytotoxicity and the degree of biochemical or histological alterations within the groups…

The Effect of Glyceryl Trinitrate on the Intravascular Oesophageal Variceal Pressure in Patients with Cirrhosis and Portal Hypertension

Glyceroltrinitrat (GTN) fuhrt zur Erschlaffung der glatten Muskulatur von Blutgefasen. Es wurde daher fur moglich gehalten, das es den Pfortaderhochdruck bei Patienten mit Leberzirrhose vermindern konnte. Mit der kurzlich beschriebenen endoskopischen Feinnadelpunktion von Osophagusvarizen konnte der Einflus von GTN auf den intravasalen Osophagusvarizendruck (IOVD) gemessen werden. Drei Minuten nach sublingualer Gabe von 2.2 mg GTN fiel der IOVD bei 10 Patienten mit Varizen Grad III von 22.8 ± 2.0 mmHg auf 12.0 ± 0.4 mmHg (p◄0.005) und bei sechs Patienten mit Varizen Grad II von 16.3 ± 0.4 mmHg auf 10.0 ± 0.4 mmHg (p◄0.005). Unsere bisherigen Ergebnisse lassen vermuten, das GTN zur Blutstill…