Possible Involvement of Intracellular Calcium-Independent Phospholipase A 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 (sPLA) type-II was previously observed in ileum of Crohn's disease (CD). Our aims were to explore the involvement of calcium-independent (i)PLAβ in the release of sPLAs from the human mast cell (MC) line (HMC-1) and investigate expressions of cytosolic (c)PLAα, iPLAβ, sPLA-IIA and sPLA-V in MCs of CD ileum. The release of sPLA was investigated in HMC-1 by immunocytochemistry and ELISA. The expression intensities of PLAs in mucosal MCs, and the proportion of PLA-positive MCs, were investigated in normal ileum and in ileum from patients with CD by immunohistochemistry. The calcium ionophore-stimulated release of sPLA-IIA and sPLA-V from HMC-1 was reduced by the iPLA-inhibitor bromoenol lactone. All four PLAs were detectable in mucosal MCs, both in normal ileum and in CD, but the proportion of iPLAβ-containing mucosal MCs and the expression intensity of sPLA-IIA was increased in CD. Results indicate that iPLAβ is involved in the secretion of sPLAs from HMC-1, and suggest that iPLAβ-mediated release of sPLA 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 PLAs in the inflammatory processes of CD.