Early Morphological Changes in Crohn’s Disease

Abstract

Recent ultrastructural investigations revealed early epithelial lesions in Crohn’s disease, while a specific morphological pattern was not identifiable. An increase in plasma cells, lymphocytes, macrophages, mast cells, eosinophilic and neutrophilic granulocytes, as well as focal edema and inflammation of tissue structures was seen in the lamina propria, submucosa and deeper layers. The results are consistent with the frequent discussion about a pathogenetically significant defect of the mucosal ‘barrier function’, which consists of mechanical, cellular, humoral, immunological and nonimmunological mechanisms, including different histotopographically defined lines of defense of the epithelium and lamina propria. An intact epithelial layer plays an important role as the first line of defense. It is evident that components of the epithelial barrier (absorptive cells, goblet cells, Paneth cells, M cells) show ultrastructural signs of alteration or injury, while the primary agent or event remains unknown. Another pathomechanism would be a preexisting defect in intestinal ‘barrier function’. Such a defect would result in an increased uptake of, or an inadequate immune reaction to, ubiquitously occurring antigens/agents (with genetic predisposition). However, no primary defect of epithelial or inflammatory cells has been definitely identified so far. Direct toxic damage of tissue secondarily introducing the inflammatory changes is also possible. Although the morphological alterations in Crohn’s disease are not yet clearly understood and exactly interpreted, transmission electron microscopy has been helpful in defining early lesions and has led to further knowledge about the pathogenesis of this disease.

Release of Mast Cell Tryptase from Human Colorectal Mucosa in Inflammatory Bowel Disease

“…Although traumatization of the tissue by sample taking contributes to the rate of initial basal release, the results obtained suggest that extracellularly located tryptase is rapidly washed out within 45 min from affected CD tissue and in amed or non-in amed UC tissue. These results are in accordance with ndings from other investigators who found either on the basis of electron microscopy, immuno-histochemistry or histamine secretion evidence for an ongoing mast cell degranulation in IBD (2,5,(10)(11)(12)(13)(14). Such an event in vivo may well explain the elevated rate of the initial basal release of tryptase in active IBD and this appears to be associated with mucosal disease activity, since in amed CD or UC tissue secretes more than double the initial basal release of tryptase than unaffected tissue.…”

“…The overall increased spontaneous tryptase secretion even in unaffected UC tissue is a striking and unexpected nding. Since mast cell numbers Scand J Gastroenterol 2001 (2) have not been quanti ed in this study, the enhanced tryptase secretion in UC indicates that either the number of secreting (activated) mast cells or the extent of activation of mast cells is generally higher than in normal colorectal mucosa. The presence of secreting mast cells in non-in amed tissue of UC is in clear contrast to the activity of other mononuclear cells, whose activity is strongly correlated to mucosal disease activity (2).…”

“…Although mast cell hyperplasia has been described in CD and UC (2,3,7), the pattern of tryptase secretion revealed no major differences between spontaneous tryptase secretion of normal gut mucosa and in amed or non-in amed IBD tissue (Fig. 1).…”

“…Although mast cell hyperplasia in the gut is a feature of IBD (2,3,6), the role of mast cells in this disease is still a matter of debate. Histologic detection of mast cells can reveal an increase in mast cell numbers, but it cannot adequately re ect their functional state of activation, since degranulated mast cells may escape from histologic assessment (6,9).…”

“…In in ammatory lesions of Crohn disease (CD) and ulcerative colitis (UC) several highly activated immune cell types have been described, including T helper 1 and T helper 2 cells, CD14-positive macrophages as well as degranulating neutrophils and eosinophils (1,2). Alterations in the number and distribution of mast cells have also been reported in IBD (2,3), but there are no data about the speci c secretory activity of human mucosal mast cells in this disorder.…”