Mast cells are an important cellular source of tumour necrosis factor α in human intestinal tissue

Abstract

BACKGROUNDSeveral inflammatory disorders of the intestine are characterised by enhanced expression of tumour necrosis factor α (TNF-α). Monocytes and macrophages have been suggested as a major cellular source of TNF-α in human gut, whereas mast cells, although known to be capable of producing TNF-α, have been poorly examined in this respect.AIMSTo investigate whether human intestinal mast cells can produce TNF-α, and which factors regulate TNF-α production in these cells.METHODSMast cells were isolated from surgery tissue specimens of patients undergoing bowel resection because of cancer. Immunohistochemical studies were performed in biopsy specimens derived from 13 patients (two healthy controls, four with Crohn’s disease, four with ulcerative colitis, three others). TNF-α mRNA and protein expression were studied in vitro by polymerase chain reaction, RNAse protection assay, western blot, and enzyme linked immunosorbent assay in isolated purified human intestinal mast cells stimulated by IgE receptor crosslinking, intestinal bacteria, and lipopolysaccharide. Cellular localisation of TNF-α was examined by immunohistochemistry.RESULTSTNF-α mRNA and protein were expressed constitutively in isolated human intestinal mast cells. Expression of TNF-α mRNA and release of TNF-α protein were substantially enhanced by IgE receptor crosslinking and by coculture of mast cells with intestinal bacteria; lipopolysaccharide had only marginal effects. Immunohistochemical studies revealed that approximately 60% of the lamina propria cells with immunoreactivity for TNF-α were mast cells.CONCLUSIONSThe data show that mast cells are an important source of TNF-α in the human intestinal mucosa.