Mucus phospholipids are decreased in ulcerative colitis. A possible clue to pathogenesis?

Aims: A defective mucus composition represents a key pathogenetic factor for intestinal injury. Phosphatidylcholine (PC) is an essential component contributing to formation of a hydrophobic mucus layer. For evaluation of phosphatidylcholine in the pathogenesis of inflammatory bowel disease, the concentration and composition of PC in the rectal mucus of patients with ulcerative colitis was determined. Electrospray ionization (ESI) tandem mass spectrometry (MS/MS) allows quantification of phosphatidylcholine species and enables us to analyze crude extracts. Methods: Lipid extracts of material obtained by light scrapings of the intestinal lumen were analyzed by nano-ESI MS/MS and with internal standardization quantified. PC and LPC species from rectoscopically acquired mucus aliquots of patients with ulcerative colitis (clinical remission) were compared to patients with Crohn's disease (clinical remission) and control subjects. Results: Patients with inactive ulcerative colitis showed significant less PC and LPC (median 346 [IQR: 230–405] pmol total PC/ mg dry weight) in rectal mucus compared to Crohn's disease (median 1126 [IQR: 465–1941] pmol total PC/ mg dry weight) and control subjects (median 1285 [IQR: 850–1639] pmol total PC/ mg dry weight) (p?<? 0.05). The molecular species of PC and LPC were not significant different in both groups. The most abundant species were PC 16: 0/18: 1; PC 16: 0/18: 2; PC 18: 0/18: 1; PC 18: 0/18: 2; LPC 16: 0; and LPC 18: 0. Conclusion: NanoESI MS/MS is a suitable tool to analyze and quantify small amounts of PC in human mucus. Patients with ulcerative colitis have significant less PC in their intestinal mucus despite a comparable PC molecular species composition pattern. This indicates that a low amount of protective mucus PC is a characteristic feature in ulcerative colitis and may predispose to an impaired mucosal barrier function facilitating inflammatory attacks by noxious colonic contents.

Schlüsselwörter

Inflammatory bowel disease - Mucus - Phospholipids