Summary
Human lymphocytes develop a de novo synthesis of nucleic acids after stimulation with phytohaemagglutinin (PHA) which is shown by an increasing incorporation of labelled precursors of purines and pyrimidines into the nucleic acids of the lymphocytes beginning at the 20th hour of the experiment. Immunosuppressive substances as l-asparaginase, prednisolone and azathioprine inhibit these de novo syntheses and, likewise, the blastogenesis of the stimulated lymphocytes and their cytoaggressive effect. Methotrexate, however, does not inhibit these reactions, although its well known effect upon the cell metabolism may also be observed with stimulated human lymphocytes. The mechanism of the immunosuppressive effect of methotrexate in vivo is yet rendered less clear by these results.
Zusammenfassung
Menschliche Lymphocyten entwickeln bei einer Stimulierung mit PHA eine de novo-Synthese von Nucleinsäuren, was sich, von der 20. Std von Versuchsbeginn an, in einem zunehmenden Einbau markierter Vorstufen von Purinen und Pyrimidinen in die Nucleinsäuren der Lymphocyten äußert. Immunosuppressiv wirkende Substanzen wie l-Asparaginase, Prednisolon und Azathioprin verhindern diese de novo-Synthesen und gleicherweise die Blastogenese der stimulierten Lymphocyten wie auch ihren cytoaggressiven Effekt. Demgegenüber verhindert Methotrexat diese Reaktionen nicht, obwohl die bekannte Wirkung von Methotrexat auf den Zellstoffwechsel auch bei stimulierten Lymphocyten beobachtet werden kann. Der Mechanismus der immunosuppressiven Wirkung von Methotrexat in vivo wird durch diese Befunde eher unklar.
Similar content being viewed by others
References
Benzio, G., Pegoraro, L., Bernengo, M. G.: Effetto del metotrexate sulla sintesi di ADN nei linfociti umani stimolati con fitoemagglutinina. Boll. Soc. ital. Biol. sper.46, 167 (1970).
Harbers, E., Domagk, G. F., Müller, W.: In: Die Nukleinsäuren. Stuttgart: Thieme 1964.
Holm, G., Perlmann, P., Werner, B.: PHA-induced cytotoxic action of normal lymphoid cells on cells in tissue culture. Nature (Lond.)203, 841 (1964).
Holm, G., Perlmann, P.: PHA-induced cytotoxic action of unsensitized immunologically competent cells on allogeneic and xenogeneic tissue culture cells. Nature (Lond.)207, 818 (1965).
Oerkermann, H., Hirschmann, W. D., Schumacher, K., Alzer, G., Uhlenbruck, G., Gross, R.: Inhibition of the cytoaggressive effect of PHA-stimulated human lymphocytes by E. coli l-asparaginase. Klin. Wschr.48, 1368 (1970).
Rosenau, W., Moon, H. D.: Lysis of homologous cells by sensitized lymphocytes in tissue culture. J. nat. Cancer Inst.27, 471 (1961).
Schwarzmeier, J., Moser, K.: Zur Frage der de novo Synthese von Adeninnucleotiden in Lymphozyten. Proc. I. Österr. Hämatol. Tagg., Wien, 1970 (in press).
Wilson, D. B.: The reaction of immunologically activated lymphoid cells against homologous target tissue cells in vitro. J. cell comp. Physiol.62, 273 (1963).
Author information
Authors and Affiliations
Additional information
This study was supported by a special grant and the Sonderforschungsbereich 68 of the Deutsche Forschungsgemeinschaft.
Rights and permissions
About this article
Cite this article
Oerkermann, H., Hirschmann, W.D. & Gross, R. Studies on the novo synthesis of nucleic acids in stimulated human lymphocytes. Klin Wochenschr 51, 471–473 (1973). https://doi.org/10.1007/BF01467754
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01467754
Key words
- de novo synthesis nucleic acids
- orotic acid
- glycine
- l-asparaginase
- methotrexate
- lymphocyte cytoaggressiveness or cytotoxicity
- lymphocyte blastogenesis