METABOLIC AND ULTRASTRUCTURAL ASPECTS OF THE INVITRO LYSIS OF CHRONIC LYMPHOCYTIC-LEUKEMIA CELLS BY GLUCOCORTICOIDS

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (4) , 1433-1440
Abstract
Human chronic lymphocytic leukemia (CLL) cells like prothymocytes and immunoactivated T lymphocytes are readily lysed in vitro by pharmacological concentrations of glucocorticoids such as cortisol, whereas peripheral blood lymphocytes and thymocytes are unaffected by the hormone. Metabolic and ultrastructural aspects of the cortisol-induced killing process of CLL cells were studied. In vitro lysis was temperature dependent and was detected only after 6-8 h incubation with cortisol by means of the trypan blue exclusion test. However, 30 min of incubation with cortisol at either 37.degree. or 4.degree. followed by the removal of the hormone was still sufficient to induce the lytic process. Ultrastructural studies demonstrated sequential changes in the cytoplasm, including swelling of mitochondria and cytoplasmic decompartmentalization, followed by loss of surface microvilli with the appearance of holes in the cell membrane, and subsequent condensation of nuclear chromatin. The large holes in the membrane appearing after 6 h of incubation with the hormone may be the cause for the penetration of the viable stain into the dead cells, as seen by light microscopy. Addition of metabolic inhibitors including actinomycin D, puromycin and cycloheximide following administration of cortisol resulted in inhibition of the cell lysis. An excess of an antagonist such as cortexolone inhibited the cortisol-induced cytolysis of the CLL cells. The glucocorticoid-induced lysis of human CLL cells may be similar to the phenomenon observed in rat or murine lymphocytes; it is probably mediated by interaction of the steroid molecule with the cytoplasmic receptor. The resulting complex appears to activate specific gene(s) the products of which eventually cause cytolysis.