Presence of group IIa secretory phospholipase A(2) in mast cells and macrophages in normal human ileal submucosa and in Crohn's disease

Secretory group IIa phospholipase A(2) (PLA(2)-II) is an important regulato r of proinflammatory lipid mediator production and may play a role in ileal inflammation in Crohn's disease. The enzyme has previously only been detec ted in epithelial Paneth cells. However, one characteristic feature of Croh n's disease is the transmural inflammation. Full thickness ileal sections f rom nine patients with Crohn's disease, and histologically normal sections from patients with colonic cancer (n=7) and chronic severe constipation (n= 1) as controls, were used in this study. PLA(2)-II-positive cells were dete cted by immunofluorescence and in situ hybridization. Metachromatic stainin g and esterase staining were used to identify mast cells and macrophages, r espectively. It was shown that mast cells and macrophages in the ileal subm ucosa in both patients and controls showed positive PLA(2)-II staining. The number of PLA(2)-II-labeled cells that did not react with metachromasia, e .g. macrophages, was significantly greater in inflamed Crohn's disease comp ared to controls. This is, to our knowledge, the first study that has descr ibed the presence in healthy, while presence and upregulation of PLA(2)-II- positive cells in inflamed human ileal submucosa. Our findings suggest a pr oinflammatory potential for secretory PLA(2)-II in submucosa, while proinfl ammatory stimulation of mast cells and macrophages in vitro has shown that the enzyme is responsible for delayed prostaglandin formation.