Abstract
Comparisons of the stimulation of normal lymphocytes and lymphoma cells by tetrameric concanavalin a (Con ta) and dimeric succinyl-Con A suggest that both stimulatory and inhibitory signals operate to modulate mitogenesis. Synergistic effects can be obtained for the stimulatory event using lectins, phorbol esters, and calcium ionophores, all of which are independently mitogenic for lymphocytes. The inhibitory effects of high doses of Con A could be mimicked by the simultaneous addition of the phorbol ester and Con A under conditions in which both reagents are optimally mitogenic when used alone. No inhibition of stimulation was found, however, when succinyl-Con A was used with phorbol ester under the same conditions. Moreover, when lymphocytes were cultured with Con A in the presence of succinyl-Con A, the inhibitory effect of the native lectin was seen at lower doses than in the absence of the derivative. These observations suggest that the stimulatory and inhibitory portions of the dose-response curve can be manipulated independently and may be mediated by two distinct signals. It is likely the signal for the inhibition of cell proliferation is regulated by the same cell surface modulating assembly that controls the mobility of cell surface receptors.
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Selected References
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- Allwood G., Asherson G. L., Davey M. J., Goodford P. J. The early uptake of radioactive calcium by human lymphocytes treated with phytohaemagglutinin. Immunology. 1971 Sep;21(3):509–516. [PMC free article] [PubMed] [Google Scholar]
- Chauvenet A. R., Scott D. W. A lectin model for unresponsiveness. I. Reversible effects of high doses of concanavalin A on spontaneous and induced DNA synthesis. J Immunol. 1975 Jan;114(1 Pt 2):470–475. [PubMed] [Google Scholar]
- Cunningham B. A., Wang J. L., Pflumm M. N., Edelman G. M. Isolation and proteolytic cleavage of the intact subunit of concanavalin A. Biochemistry. 1972 Aug 15;11(17):3233–3239. doi: 10.1021/bi00767a016. [DOI] [PubMed] [Google Scholar]
- Dent P. B. Inhibition by phytohemagglutinin of DNA synthesis in cultured mouse lymphomas. J Natl Cancer Inst. 1971 Apr;46(4):763–773. [PubMed] [Google Scholar]
- Edelman G. M., Cunningham B. A., Reeke G. N., Jr, Becker J. W., Waxdal M. J., Wang J. L. The covalent and three-dimensional structure of concanavalin A. Proc Natl Acad Sci U S A. 1972 Sep;69(9):2580–2584. doi: 10.1073/pnas.69.9.2580. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Edelman G. M., Yahara I., Wang J. L. Receptor mobility and receptor-cytoplasmic interactions in lymphocytes. Proc Natl Acad Sci U S A. 1973 May;70(5):1442–1446. doi: 10.1073/pnas.70.5.1442. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GOLDSTEIN I. J., HOLLERMAN C. E., SMITH E. E. PROTEIN-CARBOHYDRATE INTERACTION. II. INHIBITION STUDIES ON THE INTERACTION OF CONCANAVALIN A WITH POLYSACCHARIDES. Biochemistry. 1965 May;4:876–883. doi: 10.1021/bi00881a013. [DOI] [PubMed] [Google Scholar]
- Gunther G. R., Wang J. L., Edelman G. M. The kinetics of cellular commitment during stimulation of lymphocytes by lectins. J Cell Biol. 1974 Aug;62(2):366–377. doi: 10.1083/jcb.62.2.366. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gunther G. R., Wang J. L., Yahara I., Cunningham B. A., Edelman G. M. Concanavalin A derivatives with altered biological activities. Proc Natl Acad Sci U S A. 1973 Apr;70(4):1012–1016. doi: 10.1073/pnas.70.4.1012. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hadden J. W., Hadden E. M., Haddox M. K., Goldberg N. D. Guanosine 3':5'-cyclic monophosphate: a possible intracellular mediator of mitogenic influences in lymphocytes. Proc Natl Acad Sci U S A. 1972 Oct;69(10):3024–3027. doi: 10.1073/pnas.69.10.3024. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Luckasen J. R., White J. G., Kersey J. H. Mitogenic properties of a calcium ionophore, A23187. Proc Natl Acad Sci U S A. 1974 Dec;71(12):5088–5090. doi: 10.1073/pnas.71.12.5088. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mackler B. F. Effect of concanavalin A on human lymphoid cell lines and normal peripheral lymphocytes. J Natl Cancer Inst. 1972 Oct;49(4):935–941. [PubMed] [Google Scholar]
- Maino V. C., Green N. M., Crumpton M. J. The role of calcium ions in initiating transformation of lymphocytes. Nature. 1974 Sep 27;251(5473):324–327. doi: 10.1038/251324b0. [DOI] [PubMed] [Google Scholar]
- Mastro A. M., Mueller G. C. Synergistic action of phorbol esters in mitogen-activated bovine lymphocytes. Exp Cell Res. 1974 Sep;88(1):40–46. doi: 10.1016/0014-4827(74)90615-6. [DOI] [PubMed] [Google Scholar]
- Mishell R. I., Dutton R. W. Immunization of dissociated spleen cell cultures from normal mice. J Exp Med. 1967 Sep 1;126(3):423–442. doi: 10.1084/jem.126.3.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
- NOWELL P. C. Phytohemagglutinin: an initiator of mitosis in cultures of normal human leukocytes. Cancer Res. 1960 May;20:462–466. [PubMed] [Google Scholar]
- Oliver J. M., Zurier R. B., Berlin R. D. Concanavalin a cap formation on polymorphonuclear leukocytes of normal and beige (chediak-higashi) mice. Nature. 1975 Feb 6;253(5491):471–473. doi: 10.1038/253471a0. [DOI] [PubMed] [Google Scholar]
- Ralph P., Nakoinz I. Inhibitory effects of lectins and lymphocyte mitogens on murine lymphomas and myelomas. J Natl Cancer Inst. 1973 Sep;51(3):883–890. doi: 10.1093/jnci/51.3.883. [DOI] [PubMed] [Google Scholar]
- Watson J. The influence of intracellular levels of cyclic nucleotides on cell proliferation and the induction of antibody synthesis. J Exp Med. 1975 Jan 1;141(1):97–111. doi: 10.1084/jem.141.1.97. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Whitney R. B., Sutherland R. M. Enhanced uptake of calcium by transforming lymphocytes. Cell Immunol. 1972 Sep;5(1):137–147. doi: 10.1016/0008-8749(72)90091-3. [DOI] [PubMed] [Google Scholar]
- Yahara I., Edelman G. M. Modulation of lymphocyte receptor redistribution by concanavalin A, anti-mitotic agents and alterations of pH. Nature. 1973 Nov 16;246(5429):152–155. doi: 10.1038/246152a0. [DOI] [PubMed] [Google Scholar]
- Yahara I., Edelman G. M. Restriction of the mobility of lymphocyte immunoglobulin receptors by concanavalin A. Proc Natl Acad Sci U S A. 1972 Mar;69(3):608–612. doi: 10.1073/pnas.69.3.608. [DOI] [PMC free article] [PubMed] [Google Scholar]
