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M94A3239.TXT
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1994-10-25
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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).