Gastroenterology

Gastroenterology

Volume 115, Issue 4, October 1998, Pages 841-848
Gastroenterology

Alimentary Tract
Differential lamina propria cell migration via basement membrane pores of inflammatory bowel disease mucosa,☆☆

https://doi.org/10.1016/S0016-5085(98)70255-0Get rights and content

Abstract

Background & Aims: In active inflammatory bowel disease (IBD), the intestinal mucosa is infiltrated by polymorphonuclear cells (PMNs), lymphocytes, 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 mucosal samples were studied by electron microscopy. Cells migrating out of the lamina propria were investigated by immunohistochemistry and fluorescence-activated cell sorter analysis. Results: In intact IBD mucosal samples, tunnels containing cells were prominent in the lamina propria matrix, and PMNs, but not other cell types, were prominent in the epithelium. In deepithelialized mucosal samples, the basement membrane was either destroyed or contained numerous large pores. During culture of deepithelialized mucosal samples, many cells (3.3 [±0.8] × 105 · g tissue−1 · h−1) migrated out of the lamina propria via basement membrane pores. PMNs and eosinophils were prominent during the first 3 hours of culture, but T cells predominated thereafter. Macrophages also migrated, but B cells were the minority population (<2%) at all times. Conclusions: In active IBD mucosa with an intact epithelium, luminally directed migration of lamina propria cells is restricted mainly to PMNs. After loss of the epithelium, other cell types also migrate into the lumen via numerous, large, basement membrane pores.

GASTROENTEROLOGY 1998;115:841-848

Section snippets

Tissue samples

Mucosa was obtained from freshly resected intestine affected by active ulcerative colitis (n = 13), Crohn's colitis (n = 4), or Crohn's ileitis (n = 5). Thirteen patients were men, and the mean age was 52 years (±4.3). Three patients were taking no drugs, 5 were taking steroids alone, 3 mesalamine preparations alone, and 11 patients combinations of steroids with either azathioprine (n = 4), a mesalamine preparation (n = 3), both drugs (n = 2), a mesalamine and azathioprine preparation (n = 1),

Analysis of H&E-stained sections

PMNs comprised 5.2% (±2.7%) and 8.4% (±3.7%) PMNs in the lamina propria and epithelium, respectively, of IBD sections. Considerably fewer PMNs were present in the lamina propria (0.3% [±0.3%]; P < 0.05) and epithelium (0.2% [±0.2%]; P < 0.01) of normal colonic mucosal samples obtained from resection specimens.

Electron microscopy of untreated mucosal samples

Transmission electron microscopy of fresh IBD-affected mucosal samples showed prominent lamina propria channels containing cells (Figure 1).

. Transmission electron micrograph of an

Discussion

The basement membrane underlying the epithelium of the normal intestinal mucosa contains numerous discrete pores, which are in continuity with tunnels in the underlying lamina propria.1, 9 We have recently shown that during culture of normal human colonic and ileal mucosal samples that had been denuded of epithelial cells, large numbers of lymphocytes, macrophages, and eosinophils migrate via the lamina propria tunnels and basement membrane pores. Of the three types of migrating cells, T cells

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    Address requests for reprints to: Y.R. Mahida, M.D., Division of Gastroenterology, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, England. Fax: (44)115-942-2232. e-mail: [email protected].

    ☆☆

    Supported by the British Digestive Foundation (to M.E.M.). Equipment funded by the Wellcome Trust (Wellcome) was used in the electron microscopy studies.

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