       Document 0175
 DOCN  M9630175
 TI    Cyclic nucleotide phosphodiesterases from purified human CD4+ and CD8+ T
       lymphocytes.
 DT    9603
 AU    Tenor H; Staniciu L; Schudt C; Hatzelmann A; Wendel A; Djukanovic R;
       Church MK; Shute JK; Immunopharmacology Group, University of
       Southampton, UK.
 SO    Clin Exp Allergy. 1995 Jul;25(7):616-24. Unique Identifier : AIDSLINE
       MED/96131142
 AB    BACKGROUND: CD4+ and CD8+ T-lymphocytes are suggested to differentially
       affect airway inflammation in asthma. Agents which increase
       intracellular cAMP levels, such as PDE inhibitors, have been shown to
       diminish lymphocyte growth and differentiation, and to affect cytokine
       expression. Differences in the PDE isoenzyme profile between CD4+ and
       CD8+ cells might form a basis to differentially modify their functions
       by PDE inhibitors. OBJECTIVE: The study investigates and compares the
       PDE isoenzyme activity profiles of human peripheral blood CD4+ and CD8+
       T-lymphocytes. METHODS: CD4+ and CD8+ T-lymphocytes were purified (>
       98%) from peripheral blood mononuclear cells by negative selection. PDE
       isoenzyme activity profiles were investigated using PDE isoenzyme
       selective inhibitors and activators. RESULTS: In CD4+ and CD8+
       T-lymphocyte homogenates, PDE IV and PDE III activities were the
       predominant PDE isoenzyme activities at 0.5 microM cyclic nucleotide
       substrate concentrations. PDE IV was localized in the soluble fraction
       whereas PDE III was membrane bound. Low PDE I, II and V activities were
       detected. About 20% of total cAMP hydrolysing capacity at 0.5 microM
       cAMP was insensitive to PDE isoenzyme selective inhibitors and
       activators and therefore could not be assigned to PDE I-IV. The PDE
       isoenzyme pattern was not different between CD4+ and CD8+ T-lymphocytes.
       Moreover, representative inhibitors of PDE III and IV activity inhibited
       cAMP hydrolysis in soluble fractions of both T-lymphocyte subsets with
       similar potency. Enzyme kinetic analysis similarly did not reveal
       differences between CD4+ and CD8+ T-lymphocytes. CONCLUSION: Normal CD4+
       and CD8+ T-lymphocytes are likely to be equally sensitive targets for
       the effects of PDE inhibitors.
 DE    Cell Separation  CD4-Positive T-Lymphocytes/*ENZYMOLOGY  CD8-Positive
       T-Lymphocytes/*ENZYMOLOGY  Human  Isoenzymes/BLOOD  Phosphodiesterase
       Inhibitors/PHARMACOLOGY  Phosphoric Diester Hydrolases/*BLOOD
       Subcellular Fractions/ENZYMOLOGY  Support, Non-U.S. Gov't
       3',5'-Cyclic-GMP Phosphodiesterase/BLOOD  3',5'-Cyclic-Nucleotide
       Phosphodiesterase/ANTAGONISTS & INHIB/  BLOOD  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

