Migration of human intestinal lamina propria lymphocytes, macrophages and eosinophils following the loss of surface epithelial cells
Yashwant R. Mahida, Alison Galvin, Trevor Gray, S Makh, Mark McAlindon, H. F. Sewell, Daniel K. Podolsky
Abstract
Yashwant R. Mahida, Alison Galvin, Trevor Gray, S Makh, Mark McAlindon, H. F. Sewell, Daniel K. Podolsky
Abstract
Lymphocytes and macrophages are present in the normal intestinal lamina propria, separated from the epithelial monolayer by the basement membrane. There is evidence for movement of mononuclear cells through the lamina propria, entering from the systemic circulation and exiting via lymphatic channels. The goal of our studies was to investigate the capacity of cells to migrate out from the lamina propria into the lumen following the loss of surface epithelial cells. An in vitro model was therefore established in which normal human intestinal mucosal samples, denuded of the surface epithelium, were maintained in culture. Electron microscopy showed that during culture, large numbers (>2 x 10(6)/g tissue per 24 h) of cells migrated out of the lamina propria via discrete 'tunnels' which were in continuity with pores (diameter <4 microm) in the basement membrane. The emigrating cells were T cells (68.5 +/- 5.1%), macrophages (10.5 +/- 1.3%) and eosinophils (7.1 +/- 1.3%). Our studies have therefore demonstrated, for the first time, the capacity for large numbers of lymphocytes, macrophages and eosinophils to migrate out of the lamina propria, via basement membrane pores. We postulate that such emigration of cells occurs in vivo following the loss of surface epithelial cells due to injury, and could represent an important form of host defence against luminal microorganisms and also facilitate wound repair by enhancing restitution by neighbouring epithelial cells, via peptide factors.
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Lymphocytes and macrophages are present in the normal intestinal lamina propria, separated from the epithelial monolayer by the basement membrane. There is evidence for movement of mononuclear cells through the lamina propria, entering from the systemic circulation and exiting via lymphatic channels. The goal of our studies was to investigate the capacity of cells to migrate out from the lamina propria into the lumen following the loss of surface epithelial cells. An in vitro model was therefore established in which normal human intestinal mucosal samples, denuded of the surface epithelium, were maintained in culture. Electron microscopy showed that during culture, large numbers (>2 x 10(6)/g tissue per 24 h) of cells migrated out of the lamina propria via discrete 'tunnels' which were in continuity with pores (diameter <4 microm) in the basement membrane. The emigrating cells were T cells (68.5 +/- 5.1%), macrophages (10.5 +/- 1.3%) and eosinophils (7.1 +/- 1.3%). Our studies have therefore demonstrated, for the first time, the capacity for large numbers of lymphocytes, macrophages and eosinophils to migrate out of the lamina propria, via basement membrane pores. We postulate that such emigration of cells occurs in vivo following the loss of surface epithelial cells due to injury, and could represent an important form of host defence against luminal microorganisms and also facilitate wound repair by enhancing restitution by neighbouring epithelial cells, via peptide factors.
Key concepts: Lamina propria, Basement membrane, Epithelium, Biology, Cell biology, Immunology, Pathology, Medicine