Abstract
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.
Highlights
Mediators released from activated intestinal mast cells (MCs) have shown to be of pathophysiological significance in Crohn’s disease (CD) [1,2], for instance, by promoting intestinal fibrosis or by decreasing the mucosal barrier against immune-activating antigens [3,4,5]
To investigate if the expressions of independent PLA2 (iPLA2) β and cytosolic PLA2 (cPLA2) α could be further increased upon activation of the MCs, 5 × 105 HMC-1 were incubated for 48h in 1 mL culture medium with or without 25 ng/mL of TNFα
In the present study we demonstrated that the expression of secretory phospholipases A2 (sPLA2) -secretory phospholipase A2 group IIA (IIA) was higher in MCs from ileal CD mucosa compared to MCs from control patients
Summary
Mediators released from activated intestinal mast cells (MCs) have shown to be of pathophysiological significance in Crohn’s disease (CD) [1,2], for instance, by promoting intestinal fibrosis or by decreasing the mucosal barrier against immune-activating antigens [3,4,5]. MC mediators of potential relevance for inflammatory conditions include, for instance, eicosanoids [6] and other lipid mediators (i.e., platelet-activating factor and lysophospholipids) generated upon activation of one or several isoforms of the phospholipase A2 superfamily (PLA2 ) [7]. The expression of different PLA2 isoenzymes in MCs of the human intestinal mucosa is still unknown, both in the normal intestine and in CD. The PLA2 s constitute a superfamily of intracellular and secretory isoenzymes that catalyzes hydrolysis of the sn-2 ester of glycerophospholipids, thereby producing free fatty acids and lysophospholipids [7]. The high molecular weight intracellular PLA2 s, cytosolic PLA2 (cPLA2 ; named group IV PLA2 ) and calcium-independent PLA2 (iPLA2 ; named group VI PLA2 ), are ubiquitously expressed in most tissues and cell types [7]. Since cPLA2 α is AA-specific, it is generally assumed to be the major contributor to the production of inflammatory eicosanoids [8]
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