FIGURE 7.

Mast cell cPLA₂α-dependent biosynthesis of anti-anaphylactic PGE₂in vivo. A, Pla2g4a^+/+ or Pla2g4a^−/− BMMCs were subcutaneously transferred into the ears of mast cell-deficient Kit^W-sh/W-sh mice. After 2 days of reconstitution, PGE₂ levels in the ears of Kit^W-sh/W-sh mice (−), those transferred with Pla2g4a^+/+ BMMCs (+/+), and those transferred with Pla2g4a^−/− BMMCs (−/−) were quantified (mean ± S.E., n = 12, **, p < 0.01). B, IgE-sensitized Ptges^+/+ and Ptges^−/− mice were challenged with or without Ag to assess PCA reaction (mean ± S.E., n = 3; *, p < 0.05 versus replicate Ptges^+/+ mice). C, schematic diagram of the dual role of cPLA₂α in mast cells for the production of pro-allergic and anti-allergic lipid mediators. In mast cells, cPLA₂α supplies AA (via COX-1 and -2, which are omitted in the figure) to hematopoietic PGD₂ synthase (PGDS) and LTC₄ synthase (LTCS) for the biosynthesis of pro-allergic PGD₂ and LTC₄, respectively (64). In adjacent fibroblasts, AA is supplied by cPLA₂α intrinsically expressed in fibroblasts (cell autonomous pathway) and by cPLA₂α in mast cells (transcellular pathway) to mPGES-1 for the biosynthesis of anti-allergic PGE₂.