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Biochim Biophys Acta. 2005 Dec 30;1738(1-3):19-28. Epub 2005

Effects of arachidonic acid analogs on FcepsilonRI-mediated activation
of mast cells.

Nakano N, Nakao A, Uchida T, Shirasaka N, Yoshizumi H, Okumura K,
Tsuboi R, Ogawa H.
Atopy (Allergy) Research Center, Juntendo University School of
Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.

Polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA) have
been shown to modulate a number of inflammatory disorders. Mast cells
play a critical role in the initiation and maintenance of inflammatory
responses. However, the effects of PUFAs on mast cell functions have
not been fully addressed. We here-in examined the effects of PUFAs on
the high affinity IgE receptor (FcepsilonRI)-mediated mast cell
activation using RBL-2H3 cells, a rat mast cell line, that were
cultured in the medium containing palmitic acid (PA), AA, or the AA
analogs mead acid (MA) and eicosapentaenoic acid (EPA). In AA-
supplemented cells, the FcepsilonRI-mediated beta-hexosamidase and TNF-
alpha release, calcium (Ca(2+)) influx, and some protein tyrosine
phosphorylations including Syk and linker for activation of T cells
(LAT) were enhanced, whereas, in MA- or PA-supplemented cells, they
were not changed when compared with cells cultured in control medium.
In EPA-supplemented cells, the enhancements of beta-hexosamidase
release and protein tyrosine phosphorylations were observed.
Furthermore, in AA- or EPA-supplemented cells, FcepsilonRI-mediated
intracellular production of reactive oxygen species (ROS) that is
required for the tyrosine phosphorylation of LAT and Ca(2+) influx
were enhanced when compared with the other cells. Thus, preincubation
of AA or EPA augmented FcepsilonRI-mediated degranulation in mast
cells by affecting early events of FcepsilonRI signal transduction,
which might be associated with the change of fatty acid composition of
the cell membrane and enhanced production of ROS. The results suggest
that some PUFAs can modulate FcepsilonRI-mediated mast cell activation
and might affect FcepsilonRI/mast cell-mediated inflammation, such as
allergic reaction.
PMID: 16403671