Possible Involvement of Intracellular Calcium-Independent Phospholipase A₂ in the Release of Secretory Phospholipases from Mast Cells-Increased Expression in Ileal Mast Cells of Crohn's Disease.

Increased activity of secretory phospholipases A₂ (sPLA₂) type-II was previously observed in ileum of Crohn's disease (CD). Our aims were to explore the involvement of calcium-independent (i)PLA₂β in the release of sPLA₂s from the human mast cell (MC) line (HMC-1) and investigate expressions of cytosolic (c)PLA₂α, iPLA₂β, sPLA₂-IIA and sPLA₂-V in MCs of CD ileum. The release of sPLA₂ was investigated in HMC-1 by immunocytochemistry and ELISA. The expression intensities of PLA₂s in mucosal MCs, and the proportion of PLA₂-positive MCs, were investigated in normal ileum and in ileum from patients with CD by immunohistochemistry. The calcium ionophore-stimulated release of sPLA₂-IIA and sPLA₂-V from HMC-1 was reduced by the iPLA₂-inhibitor bromoenol lactone. All four PLA₂s were detectable in mucosal MCs, both in normal ileum and in CD, but the proportion of iPLA₂β-containing mucosal MCs and the expression intensity of sPLA₂-IIA was increased in CD. Results indicate that iPLA₂β is involved in the secretion of sPLA₂s from HMC-1, and suggest that iPLA₂β-mediated release of sPLA₂ 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 PLA₂s in the inflammatory processes of CD.

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