Document 3239
 DOCN  M94A3239
 TI    Polyunsaturated fatty acids reduce gp120-induced syncytia formation.
 DT    9412
 AU    Aloia RC; Tian HR; Mlekusch W; VanGent CM; Jensen FC; Anesthesia
       Service, J.L. Pettis Veterans Hospital, Loma Linda, CA; 92357.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):121 (abstract no. PA0102). Unique
       Identifier : AIDSLINE ICA10/94369336
 AB    OBJECTIVE: We have previously demonstrated that the anti-Leu3A mAb-
       inhibitable fusion between 8E5 cells, carrying the HIV genome (minus the
       pol gene) and bearing gp120, with Molt3 cells expressing CD4+ receptors,
       was significantly reduced after treating the cells with the long chain,
       polyunsaturated fatty acid, docosahexaenoic acid (22:6, n-3), but not
       with the monounsaturated, oleic acid (18:1, n-9; Aloia et al, VIII
       International Congress on AIDS; PoA 2455). Fusion was also blocked using
       the cholesterol inhibitor, 25-hydroxycholesterol, and local anesthetics
       (Aloia et al, IX International Congress on AIDS; WS-A01-6). We have
       since found that Molt4-clone8 cells are capable of forming giant
       syncytia of 50 to > 100 fused cells (compared to the 3-10 cell syncytia
       formed with Molt3 cells) and have used Molt4 cells to explore the
       influence of a host of polyunsaturated fatty acids on syncytia
       formation. METHODS: 8E5 cells and Molt4 cells were mixed (1.2:2;
       density, 1 x 10(6) cells/ml), incubated 5 hrs. at 37 degrees C and
       syncytia formation evaluated in control cells and those pre-treated with
       fatty acids for 72 hrs. The fatty acids evaluated were: linoleic acid
       (18:2, n-6); linolenic acid (18:3, n-3); and, arachidonic acid (20:4,
       n-6). These fatty acids were compared with docosahexaenoic acid (22:6,
       n-3) and oleic acid (18:1, n-9) from our previous studies.
       Concentrations of fatty acids used (< 25 microM) were shown to have no
       effect on growth and viability of the cells or to inhibit cell growth by
       < 10%. RESULTS: Pre-treatment of target Molt4-clone8 cells with each
       polyunsaturated fatty acid for 72 hours prior to exposure to the
       gp120-bearing, 8E5 cells caused a significant reduction (> 75%) in the
       size of syncytia formed compared to control cells not pre-treated with
       fatty acid. Further, as shown with Molt3 cells, fusion of Molt4 cells
       with 8E5 cells was unaffected by pre-treatment with 18:1 (n-9).
       CONCLUSIONS: Our results indicate that polyunsaturated fatty acids and
       other agents which may alter membrane lipids and/or fluidity reduce the
       degree of fusion between gp120 expressing 8E5 cells and the
       CD4(+)-expressing Molt3 and Molt4-clone 8 cells.
 DE    Antigens, CD/METABOLISM  Antigens, CD4/METABOLISM  Cell Division/DRUG
       EFFECTS  Cell Fusion/DRUG EFFECTS  Cell Line  Cell Survival/DRUG EFFECTS
       Clone Cells  Comparative Study  Fatty Acids, Nonesterified/*PHARMACOLOGY
       Fatty Acids, Unsaturated/*PHARMACOLOGY  Giant Cells/*DRUG
       EFFECTS/PHYSIOLOGY  Human  HIV Envelope Protein gp120/*METABOLISM
       Membrane Fluidity  Tumor Cells, Cultured  MEETING ABSTRACT

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