Immune regulatory effect of hepatic factor associated with thymus alteration.
ABSTRACT This study was carried out to clarify the mechanism of the immune regulatory effect of factors which were liberated from the ischemic damaged liver. By occlusion of the hepatic vessels (hepatic artery and portal vein) for 40 min daily during 5 days to induce the ischemic damage of the liver, reduced thymus weight (50 +/- 5 mg; control, 274 +/- 23 mg) and cell count (0.7 +/- 0.3 X 10(7); control, 3.5 +/- 0.3 X 10(8] and complete differentiation of thymocytes were observed, i.e., helper cells reacting to monoclonal antibody W3/25 were 34 +/- 8% and suppressor/cytotoxic cells to OX-8, 49 +/- 5% (in control W3/25:89 +/- 1%, OX-8:89 +/- 1%). These quantitative and qualitative changes of thymocytes were correspondent to those of animals treated with 40 mg CsA/kg per day for 5 days; however, medication with 10 mg prednisolone/day 5 times could not induce any alteration of thymocyte subpopulation (W3/25:89 +/- 1%, OX-8:87 +/- 1%) although the weight and cell count decreased to 92 +/- 8 mg and 4.1 +/- 0.6 X 10(7), respectively. Furthermore, 5 days after liver allotransplantation (BDE to LEW), the weight and cell count of the thymus were extremely reduced (58 +/- 6 mg, 2.7 +/- 0.2 X 10(7], and thymocyte differentiation was observed (W3/25:56.6%, OX-8:61 +/- 11%). On the other hand, in heart transplantation the atrophy of the thymus was not so strong (105 +/- 28 mg, 1.3 +/- 0.6 X 10(8], and there was no change in the subpopulation (W3/25:89 +/- 2%, OX-8:88 +/- 1%).(ABSTRACT TRUNCATED AT 250 WORDS)
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ABSTRACT: These studies demonstrate the presence of an immunosuppressive and cytotoxic factor in the perfusate of ischemic damaged liver. A BDE rat liver perfusate (LP) was prepared after 6 h warm ischemia by intraportal perfusion with 2 ml/g of Ringer's solution (one time-LP1 or five times-LP5 with the same volume of solution). Protein amount of LP1 and LP5 was 0.9 and 2.8-3.9 mg/ml. In vivo activity of the hepatic perfusates was studied by effect on renal allograft survival time. LEW rats with BDE kidney transplant, treated daily with 2 ml of LP1 for 5 days, starting on the day of grafting, survived 8.9 +/- 1.8 days, significantly longer than control animals (6.5 +/- 0.5 days). After administration of LP5 renal recipients survived 10.3 +/- 1.3 days and when the treatment with LP5 was prolonged to 10 days animals survived 9-34 days (mean 15.3 +/- 7.3 days). The presence of the suppressive factor was also studied in renal, spleen and heart extracts, prepared after 6 h warm ischemia. Protein amount of extracts was adjusted to 3-4 mg/ml by Ringer's solution. Immunosuppressive activity of LP and other organ extracts was tested in vitro by their influence on MLC reaction (LEW and BDE lymphocytes) and on LEW cells in the PHA stimulation assay. Lymphocyte blastogenic response on MLC reaction and in culture with PHA was strongly inhibited by LP but weakly by organ extracts. Hepatic perfusates were cytotoxic against lymphocytes and fibroblasts in a three day cultures. Cytotoxic activity of the organ extracts was lower than LP. Extract of the cold preserved kidneys showed immunosuppressive and cytotoxic effect like extract of ischemically injured kidneys but smaller than LP. After heat inactivation at 70 degrees C the activity of hepatic perfusate decreased. Immunosuppressive organ factor (IOF) seems to be a normal cell component, not a decomposition product of the ischemically damaged hepatic tissue.Research in Experimental Medicine 02/1981; 179(1):69-80.
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ABSTRACT: The blastogenic and DNA synthetic response of human peripheral blood lymphocytes (PBL) to phytohemagglutinin (PHA) and allogeneic cells can be inhibited by a nontoxic aqueous extract (LEx) of normal human liver. LEx reversibly inhibits the activation of PBL by PHA, arrests ongoing DNA synthesis, and limits the duration of the DNA synthetic response to PHA at concentrations as low as 0.7 to 1.5 microgram LEx protein/culture. In contrast, human T lymphocyte E rosette formation is unaffected by LEx concentrations in excess of 900 microgram/culture. LEx has been partially purified by ultracentrifugation, ammonium sulfate precipitation, and molecular exclusion chromatography and appears to be a heat labile protein with a m.w. of approximately 65,000 and an isoelectric point of approximately 4.08. LEx is distinct from other previously described human immunoregulatory molecules and is potentially releasable in vivo from injured or necrotic liver cells. Because of its potency and anatomic distribution LEx may potentially modulate immunopathogenetic events responsible for assorted inflammatory and neoplastic liver diseases.The Journal of Immunology 11/1978; 121(4):1279-86. · 5.52 Impact Factor
- Transplantation 07/1984; 37(6):631-3. · 3.78 Impact Factor