ABSTRACT
Human ceruloplasmin was shown to have a restorative effect on the decrease of delayed hypersensitivity in sarcoma-180-bearing mice and of helper T-cell activity in cell-free. Ehrlich cancerous ascitic fluid-treated mice. Furthermore, it was also shown that ceruloplasmin augments the in vivo generation of alloreactive cytotoxic cell which consist of cytotoxic T-lymphocytes, cytotoxic macrophages and K cells.
Subject(s)
Adjuvants, Immunologic , Carcinoma, Ehrlich Tumor/immunology , Catalase/antagonists & inhibitors , Ceruloplasmin/pharmacology , Endotoxins/pharmacology , Killer Cells, Natural/immunology , Neoplasm Proteins/pharmacology , Sarcoma 180/immunology , T-Lymphocytes/immunology , Animals , Antibody-Dependent Cell Cytotoxicity , Female , Hypersensitivity, Delayed , Killer Cells, Natural/drug effects , Mice , Mice, Inbred Strains , T-Lymphocytes/drug effectsABSTRACT
Human ceruloplasmin was found to have a neutralizing effect against the toxohormone activities of the basic protein isolated from Ehrlich carcinoma cells; this basic protein decreases the levels of serum iron and liver catalase activity upon intraperitoneal injection into mice and shows direct cytotoxicity toward normal mouse lymphocytes and macrophages. Furthermore, it was also shown that ceruloplasmin has antitumor activity against sarcoma-180 cells implanted in ICR mice.
Subject(s)
Antineoplastic Agents/pharmacology , Catalase/antagonists & inhibitors , Ceruloplasmin/pharmacology , Endotoxins/antagonists & inhibitors , Neoplasm Proteins/antagonists & inhibitors , Animals , Female , Humans , Iron/blood , Liver/enzymology , Mice , Sarcoma 180/drug therapyABSTRACT
LB, the antitumor protein whose level is increased in the serum of OK-432-treated mice, was identified as hemopexin, which is a serum beta-glycoprotein having a heme-binding capability. When incubated with heme, LB showed several absorption maxima in the ultraviolet and visible regions, and the addition of dithionite increased the extinction of the Soret band, which was shifted to a longer wavelength. The ultraviolet circular dichroism spectrum of LB exhibits a positive maximum at 292 nm and a shoulder near 280 nm. The far ultraviolet CD spectrum of LB has a prominent positive maximum at 231 nm. These spectral characteristics are identical with those of rabbit, rat or human hemopexin. In addition, the relative mobility on polyacrylamide gradient gel electrophoresis and the results of amino acid analysis ae in very good agreement with results obtained previously for rabbit and human hemopexins. Since LB has enhancing effects on the tumor cell killing and binding by OK-432-elicited macrophages, these results strongly imply that the increase of hemopexin in serum plays an important role in the host-mediated antitumor activity of certain antitumor drugs.
