Structural abnormalities of jejunal epithelial cell membranes in celiac sprue
Madara, J.L.; Trier, J.S.
Laboratory Investigation; A Journal of Technical Methods and Pathology 43(3): 254-261
1980
ISSN/ISBN: 0023-6837 PMID: 7401635 Document Number: 167434
Microvillus intramembrane particles (IMPs), thought to represent integral membrane proteins, increase from crypt to villus in concert with increases in the specific activities of several brush border enzymes. Tight junction (TJ) structure, which generally correlates with epithelial permeability, is less organized between crypt cells than between villus absorptive cells. IMP density and TJ structure in celiac sprue, a disease characterized structurally by hyperplastic crypts and shortened villi with damaged surface cells and functionally in part by a decrease in specific activities of several brush border enzymes and an increase in mucosal permeability to large molecules and net intestinal fluid secretion, are examined. Freeze fracture replicas of jejunal mucosa from 8 patients with celiac sprue were examined. In 4 patients from whom the most material was available, IMP density and TJ structure were quantitatively analyzed from low crypt to absorptive surface. For comparison, data were obtained from freeze-fracture replicas of normal human proximal jejunum. IMP density was similar in control and celiac sprue crypts. Although celiac sprue surface absorptive cells had IMP densities higher than crypt cells, they had approximately 30% fewer IMP than control villus absorptive cells. No quantitative differences in TJ structure existed between control and celiac sprue crypts. Celiac sprue surface cells had TJ with fewer strands and less depth than those between control villus absorptive cells. Damaged surface cell TJ also displayed qualitative structural abnormalities such as strand discontinuities and lateral aberrant strands. Rare complementary replicas of P-faces showed focal gaps up to 50 nm. in some celiac sprue absorptive cell TJ; thus, the structural barricade which normally separates the lumen from the paracellular space was focally disrupted. In celiac sprue, IMP density correlates with the decrease in specific activity of brush border enzymes. There is an expanded population of crypt-type TJ. TJ between damaged surface cells are structurally abnormal. These TJ abnormalities may contribute to alterations in intestinal permeability in celiac sprue.