Role of anions in the lymphocytolytic action of corticosteroids and fatty acids.
Rat thymocytes were exposed in vitro to the corticosteroid dexamethasone, 10 nM, for 10 min, or to oleic acid, 500 nM for 2 min. This results in cytolysis after 6 hr, if incubation is continued. Instead, the cells were centrifuged, the supernatant fluid decanted, and the cells subjected to osmotic shock in 1.5 mM MgCl2. The naked nuclei were incubated at 37 degrees C and examined by light and electron microscopy. Nuclear edema was evident early, and most nuclei showed damage with variation in shape and size and distinct folds, which was maximal by 1-2 hr as a result of these treatments. This was true also if nuclei were incubated in MgF2 or Mg(NO3)2 but not in MgBr2, MgI2, MgSO4 or Mg-citrate. Spleen lymphocyte nuclei showed similar damage but only after incubation with 20 microM oleic acid, and not at all with corticosteroids. The effects of both steroid and fatty acid, even at greatly increased concentrations, were inhibited by tri-n-butyl tin chloride, 10 microM, and by 4-4'-diisothiocyanostilbene-2,2'-disulfonic acid, sodium salt, 10 microM, both of which block chloride ion transport. It is concluded that the cytolytic effects of both corticosteroids and free fatty acids involve influx of chloride ion resulting in nuclear edema, which subsequently leads to fragmentation of chromatin, karyorrhexis and, ultimately, cytolysis.
D000818:Animals; D000838:Anions; D002467:Cell Nucleus / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D008214:Lymphocytes / Q000187:drug effects*; D008854:Microscopy, Electron; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology*; D051381:Rats; D013154:Spleen; D013950:Thymus Gland
D000838:Anions; D009829:Oleic Acids; D019301:Oleic Acid; D003907:Dexamethasone