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. 1998 Apr;42(4):522–529. doi: 10.1136/gut.42.4.522

Expression of cell membrane complement regulatory glycoproteins along the normal and diseased human gastrointestinal tract

A Berstad 1, P Brandtzaeg 1
PMCID: PMC1727075  PMID: 9616315

Abstract

Background/Aims—Uncontrolled complement activation may be of immunopathological importance in inflammatory diseases of the gastrointestinal tract. Expression of membrane bound factors that regulate complement activation was therefore studied in situ. 
Methods—Frozen tissue specimens were obtained from patients with Helicobacter pylori gastritis, coeliac disease, Crohn's disease, or ulcerative colitis, and from histologically normal controls. Sections were examined by immunofluorescence with monoclonal antibodies to protectin (CD59), decay accelerating factor (DAF), and membrane cofactor protein (MCP). 
Results—Protectin and MCP were widely expressed in normal and diseased mucosae. MCP was generally observed basolaterally on all epithelial cells, whereas apical protectin expression was more intense on the epithelium of normal colonic mucosa than in the normal duodenum (p = 0.001). Epithelial DAF and to some extent protectin were upregulated in gastritis, coeliac disease, and inflammatory bowel disease. Areas of the stomach with intestinal metaplasia expressed DAF, unlike the adjacent gastric epithelium. Parietal cells of the gastric body expressed neither protectin nor DAF. 
Conclusion—Epithelial complement inhibitory molecules were expressed differently at various normal gastrointestinal sites and also in association with mucosal disease, suggesting variable protective potential. Such molecules could play a role in the development of gastric atrophy by protecting areas of intestinal metaplasia. Conversely, parietal cells appeared to be potentially vulnerable targets for complement attack. 



Keywords: Helicobacter pylori; coeliac disease; Crohn's disease; ulcerative colitis; immunofluorescence; complement regulatory proteins

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Figure 1 .

Figure 1

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Immunofluorescence staining for protectin (CD59) in cryosections of mucosal tissue specimens. (A) In the normal stomach, CD59 is present in vessel endothelium (bowed arrow), extravascular tissue elements, and apically on epithelial cells of gastric body pits (arrow). (B) Parietal cells (arrow) show autofluorescence but do not express CD59. (C) In distal duodenum with coeliac disease (total villous atrophy) there is notable apical and some basolateral expression of CD59 on the surface epithelium (at the top) as well as on lamina propria cells (basement membrane indicated by broken line). (D) In crypts (bowed arrow) of normal colon, there is strong apical and weaker basolateral expression of CD59 on enterocytes but apparently not on goblet cells. Note also strong expression in the lamina propria. Original magnifications: A, B, and D, × 400; C, × 1000.


Figure 2 .

Figure 2

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(A) Immunofluorescence for DAF (CD55) in sections of ethanol fixed specimen from the gastric antrum of a patient with H pylori infection, gastric ulcer, and extensive metaplasia. (B) Adjacent haematoxylin and eosin stained section shown for morphological orientation. The foveolar pit on the left shows intestinal metaplasia, with apical CD55 expression on enterocytes, whereas goblet cells (arrow) are negative, producing a gap in the fluorescent luminal brim. Gastric pit epithelium elsewhere in the section is completely CD55-negative. Original magnifications: A and B, × 400. 


Figure 3 .

Figure 3

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Two colour immunofluorescence staining for DAF (CD55, Texas red) and factor VIII related antigen (FITC, green) in cryosection from inflamed colon of patient with Crohn's disease (A) or from distal duodenum of a patient with coeliac disease (B). Notable apical CD55 expression is seen on the colonic surface epithelium and on duodenal crypt epithelium (basement membrane indicated by broken line). Subepithelial blood vessels, identified by the expression of von Willebrand factor, do not express CD55 in either tissue. Original magnification: A and B, × 1000. 


Figure 4 .

Figure 4

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Immunofluorescence staining of MCP (CD46) in mucosal sections. (A) In normal colonic mucosa, vascular endothelium (arrow), extravascular tissue (M), and in particular epithelial cells show intense CD46 expression. (B) Distinct basolateral expression of CD46 is evident on parietal cells in inflamed gastric body mucosa. Original magnifications: A, × 250; B, × 400. 


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