Possible Involvement of Intracellular Calcium-Independent Phospholipase A 2 in the Release of Secretory Phospholipases from Mast Cells-Increased Expression in Ileal Mast Cells of Crohn's Disease.

Increased activity of secretory phospholipases A ₂ (sPLA ₂ ) type-II was previously observed in ileum of Crohn's disease (CD). Our aims were to explore the involvement of calcium-independent (i)PLA ₂ β in the release of sPLA ₂ s from the human mast cell (MC) line (HMC-1) and investigate expressions of cytosolic (c)PLA ₂ α, iPLA ₂ β, sPLA ₂ -IIA and sPLA ₂ -V in MCs of CD ileum. The release of sPLA ₂ was investigated in HMC-1 by immunocytochemistry and ELISA. The expression intensities of PLA ₂ s in mucosal MCs, and the proportion of PLA ₂ -positive MCs, were investigated in normal ileum and in ileum from patients with CD by immunohistochemistry. The calcium ionophore-stimulated release of sPLA ₂ -IIA and sPLA ₂ -V from HMC-1 was reduced by the iPLA ₂ -inhibitor bromoenol lactone. All four PLA ₂ s were detectable in mucosal MCs, both in normal ileum and in CD, but the proportion of iPLA ₂ β-containing mucosal MCs and the expression intensity of sPLA ₂ -IIA was increased in CD. Results indicate that iPLA ₂ β is involved in the secretion of sPLA ₂ s from HMC-1, and suggest that iPLA ₂ β-mediated release of sPLA ₂ from intestinal MCs may contribute to CD pathophysiology. Ex vivo studies on isolated mucosal mast cells are however needed to clarify the precise role of MC PLA ₂ s in the inflammatory processes of CD.