Carrageenans, highly sulfated polysaccharides and macrophage-toxic agents: newly found human T lymphocyte mitogens.
We obtained the following results, using carrageenans (CGNs) of three types (kappa, lambda and iota), macrophage-toxic agents. 1. CGNs were toxic to human monocytes, cytotoxicity varying from 40% to 60%, as judged by trypan blue dye exclusion test. 2. CGNs were proved to be newly found mitogens for human T cells, whereas CGNs are polyclonal B-cell activators in mice and induced DNA synthesis that peaked at days 6 or 7. In addition, iota CGN induced an early peak of 3H-thymidine uptake at day 1, which found out to be cytoplasmic uptake of 3H-thymidine. 3. Only lambda and iota CGN induced slightly higher DNA synthesis in purified B cells, but both failed to induce polyclonal antibody synthesis in B cells. 4. In spite of the fact the CGNs are macrophage-toxic agents, CGNs could induce Il-1 production by the surviving monocytes. Thus CGN-induced human T-cell activation requires a relatively smaller number of monocytes. 5. The mitogenic responses of T cells induced by kappa, lambda and iota CGN were significantly inhibited by cyclosporin A (CyA) treatment (250 ng/ml) and Con A and PHA responses were also inhibited by CyA addition. It was concluded that CGNs were newly found human T-cell mitogens, which is in sharp contrast with polyclonal B-cell activators in mice, and the mechanism of T-cell activation induced by CGNs was the same as that by Con A or PHA, though there may be another possibility of inhibition mechanism by CyA.
D001402:B-Lymphocytes / Q000276:immunology; D002351:Carrageenan / Q000494:pharmacology*; D003524:Cyclosporins / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008934:Mitogens / Q000494:pharmacology*; D011134:Polysaccharides / Q000032:analysis / Q000494:pharmacology; D000461:Rhodophyta / Q000032:analysis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D003524:Cyclosporins; D008934:Mitogens; D011134:Polysaccharides; D002351:Carrageenan; D004247:DNA