NO as a Physiological Signal Molecule that Triggers Thymocyte Apoptosis

  • Karin Fehsel
  • Klaus-Dietrich Kröncke
  • Victoria Kolb-Bachofen
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 387)


Nitric oxide (NO) produced at high concentrations by the inducible NO synthase (iNOS) is an important effector molecule involved in immune regulation and defence. In in vitro experiments we could show that NO represents a signal for triggering apoptosis in 30% of thymocytes with a concomittant decrease in CD4+CD8+ cells. In addition it protects the remaining cell population from apoptosis induced by glucocorticoids comparable to the protective effect of heat shock.

NO-induced DNA-strand breaks led to increased expression of p53, as detected by PCR analysis 2h after NO donor addition.

Furthermore, in cocultures of thymocytes with NO-producing endothelial cells the rate of thymocyte apoptosis was significantly increased, and this could be completely prevented by inhibiting NO production. Addition of dexamethasone to these cocultures did not lead to a further increase in the percentage of apoptotic thymocytes, underlining the protective effect of NO on dexamethasone-induced apoptosis.


Nitric Oxide Nick Translation Murine Peritoneal Macrophage Thymocyte Apoptosis Apoptotic Thymocyte 
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  1. 1.
    Fehsel K., V. Kolb-Bachofen, and H. Kolb. 1991. Analysis of TNFÂ-induced DNA strand breaks at the single cell level. Am. J. Path. 139: 251.PubMedGoogle Scholar
  2. 2.
    Thomas D.J., and T.C. Caffrey. 1991. Lipopolysaccharide induces double-stranded DNA fragmentation in mouse thymus: protective effect of zinc treatment. Toxicology 68: 327.PubMedCrossRefGoogle Scholar
  3. 3.
    Fehsel K., K.-D. Kröncke, H. Kolb, and V. Kolb-Bachofen. 1993. In situ nick translation detects focal apoptosis in thymuses of glucocorticoid-and LPS-treated mice. J. Histochem. Cytochem. 42: 613.CrossRefGoogle Scholar
  4. 4.
    Migliorati G., I. Nicoletti, F. Crocicchio, C. Pagliacci, F. D’Adamio, and C. Riccardi. 1992. Heat shock induces apoptosis in mouse thymocytes and protects them from glucocorticoid-induced cell death. Cell. Immunol. 143: 348.PubMedCrossRefGoogle Scholar
  5. 5.
    Albina J.E., S. Cui, R.B. Mateo, and J.S. Reichner. 1993. Nitric oxide-mediated apoptosis in murine peritoneal macrophages. J. Immunol. 150: 5080.PubMedGoogle Scholar
  6. 6.
    Cui S., J.S. Reichner, and J.E. Albina. 1994. Nitric oxide (NO) induces apoptosis in ConA-stimulated splenocytes. FASEB J. 8: 4470.Google Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Karin Fehsel
    • 1
  • Klaus-Dietrich Kröncke
    • 1
  • Victoria Kolb-Bachofen
    • 1
  1. 1.The Institute of Immunobiology and Biomedical Research Center Department of MedicineHeinrich-Heine-UniversityDüsseldorfGermany

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