title: Membrane fluidity and cholesterol in thymus and spleen cells from mice treated with immunomodulatory drugs.
abstract: We have used spin labeling, fluorescence polarization, and chemical analysis to characterize membrane properties of thymocytes from mice treated with immunomodulatory drugs. The number of thymocytes was reduced 90-95% by treatment of 6-9 week old mice with hydrocortisone acetate (HCA) or methylprednisolone (both 125 mg/kg) or with cyclophosphamide (250 mg/kg). Electron spin resonance (esr) examination of thymocytes labeled with 5-nitroxyl stearic acid indicated that the membranes of cells remaining after treatment with any of these drugs were more rigid than those from saline-treated controls. The total cholesterol/phospholipid (C/PL) molar ratio of the HCA-resistant thymocytes was twice that of the control mice. Treatment of mice with other immunomodulatory drugs, cyclophosphamide, cytosine arabinoside (Ara-C), 2-amino-5-bromo-6-phenyl-4-(3H)-pyrimidinone (ABPP) and 15(S)-methyl prostaglandin E1 (15(S)-methyl PGE1), also altered the C/PL ratio in thymocytes and, in some cases, in spleen cells. Fluorescence polarization measurements of thymocytes labeled with 1,6-diphenyl-1,3,5-hexatriene (DPH) did not reveal the differences between cells from HCA-and saline-treated mice that were detected by spin labeling and chemical analysis. Our results indicate that the greater rigidity detected by spin labeling of hydrocortisone-resistant thymocytes may be due, at least in part, to greater membrane cholesterol content. Of the methods employed, chemical analysis was the most sensitive in revealing drug-induced alterations in thymocyte populations.
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives*; D000818:Animals; D002462:Cell Membrane / Q000032:analysis / Q000187:drug effects; D002784:Cholesterol / Q000032:analysis*; D003520:Cyclophosphamide / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011459:Prostaglandins E, Synthetic; D011743:Pyrimidines / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D013154:Spleen / Q000032:analysis / Q000166:cytology / Q000187:drug effects*; D013950:Thymus Gland / Q000032:analysis / Q000166:cytology / Q000187:drug effects*
chemical_list: D007166:Immunosuppressive Agents; D011459:Prostaglandins E, Synthetic; D011743:Pyrimidines; D003561:Cytarabine; C025170:15(S)-15-methylprostaglandin E1; C021650:hydrocortisone acetate; C014927:2-amino-5-bromo-6-methyl-4-pyrimidinol; D003520:Cyclophosphamide; D002784:Cholesterol; D000527:Alprostadil; D006854:Hydrocortisone; D008775:Methylprednisolone