DIFFERENTIAL LAMINA PROPRIA CELL-MIGRATION VIA BASEMENT-MEMBRANE PORES OF INFLAMMATORY BOWEL-DISEASE MUCOSA

Background & Aims: In active inflammatory bowel disease (IBD), the int estinal mucosa is infiltrated by polymorphonuclear cells (PMNs), lymph ocytes, and monocytes from the systemic circulation. Using an ex vivo model, we have investigated luminally directed migration of cells out of the lamina propria. Methods: Fresh untreated and deepithelialized m ucosal samples were studied by electron microscopy. Cells migrating ou t of the lamina propria were investigated by immunohistochemistry and fluorescence-activated cell sorter analysis. Results: In intact IBD mu cosal samples, tunnels containing cells were prominent in the lamina p ropria matrix, and PMNs, but not other cell types, were prominent in t he epithelium. In deepithelialized mucosal samples, the basement membr ane was either destroyed or contained numerous large pores. During cul ture of deepithelialized mucosal samples, many cells (3.3 [+/-0.8] x 1 0(5) . g tissue(-1) . h(-1)) migrated out of the lamina propria via ba sement membrane pores. PMNs and eosinophils were prominent during the first 3 hours of culture, but T cells predominated thereafter. Macroph ages also migrated, but B cells were the minority population (< 2%) at all times. Conclusions: In active IBD mucosa with an intact epitheliu m, luminally directed migration of lamina propria cells is restricted mainly to PMNs. After loss of the epithelium, other cell types also mi grate into the lumen via numerous, large, basement membrane pores.