Immunosuppresive effect of a human hepatic glycoferroprotein, alpha2H globulin. A study on the transformation of normal human lymphocytes.
A macroglycoferroprotein of hepatic orgin, alpah2H globulin, the serum level of which increases a few weeks or months before local recurrence of metastases, has been essayed for its immunosuppressive activity. The study was carried out using the lymphoblastic transformation test and was judged by tritiated thymidine incorporation and microscopic examination. PHA-induced blast transformation of 97 per cent of normal donor lymphocytes is inhibited by 100 mug/ml of alpha2H globulin. This inhibitory effect is proportional to the quantity of added alpha2H globulin. In is obvious with a concentration of 2-5 mug/ml, a frequently observed level in the serum of patient with tumours. Preincubation of lymphocytes with alpha2H globulin renders more effective the inhibitory action on PHA-induced transformation. A mechanism of competition between PHA and alpha2H globulin is suggested by preincubation and the inhibitory effect related to the doses. However, microscopic observation shows that alpha2H globulin acts on the earliest events occurring to the stimulated lymphocytes, by inhibiting cytoplasmic RNA and protein synthesis. The alpha2H globulin effect may not only have an immunosuppresive activity but it may have a more general effect, for example blocking or modifying cellular respiration.
D000510:Alpha-Globulins; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D005296:Ferrous Compounds / Q000494:pharmacology*; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D007165:Immunosuppression Therapy; D007501:Iron / Q000494:pharmacology*; D037102:Lectins / Q000494:pharmacology; D008099:Liver / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008259:Macroglobulins / Q000494:pharmacology*; D009362:Neoplasm Metastasis; D010101:Oxygen Consumption; D014176:Protein Biosynthesis; D012313:RNA / Q000037:antagonists & inhibitors
D000510:Alpha-Globulins; D005296:Ferrous Compounds; D006023:Glycoproteins; D037102:Lectins; D008259:Macroglobulins; D012313:RNA; D004247:DNA; D007501:Iron