Lysozyme expression in microscopic colitis
ABSTRACT To audit the cellular expression of the innate antibacterial enzyme lysozyme in colonic biopsies from a cohort of patients having microscopic colitis (MC-collagenous colitis (CC) or lymphocytic colitis (LC)). Results were compared with those recorded in patients with inflammatory bowel disease (IBD) of the colon (ulcerative colitis (UC) or Crohn's colitis).
Fifty-five consecutive cases having biopsies from the left colon were investigated: 27 MC (14 CC and 13 LC) and 28 IBD (14 UC and 14 Crohn's colitis). Sections were stained with antilysozyme antibody. Twelve cases (3 CC, 3 LC, 3 UC and 3 Crohn's colitis) were challenged with the macrophage marker CD68 (clone PG-M1).
In MC, marked lysozyme expression in the colonic crypts was recorded in CC (p<0.05). The number of cases with metaplastic Paneth cells was higher in CC than in LC (p<0.05). In IBD, only active Crohn's colitis displayed marked lysozyme expression in the colonic crypts. Marked lysozyme immune-reactivity in subepithelial lamina propria mucosa (lpm) macrophages was found in LC (LC vs CC p<0.05).
The increased production of the antibacterial enzyme lysozyme in CC and LC supports a bacterial aetiology for these two diseases. Lysozyme upregulation in different cell types (epithelial vs macrophages) supports the notion that CC and LC might be two different maladies.
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ABSTRACT: Lysozyme is as an innate enzyme with potent antibacterial properties found in Paneth cells in normal duodenal crypts. Since celiac disease concurs with an abnormal duodenal microbiota we explored the expression of lysozyme in this disease. Fifty-three duodenal biopsies were stained with anti-lysozyme: 15 had normal duodenal mucosa (NDM), 7 chronic active duodenitis (CAD), 3 borderline (BL), 17 subtotal villous atrophy (SVA) and 11 total villous atrophy (TVA). NDM showed lysozyme-positive Paneth cells arranged in "Indian file" in 93.3%. In contrast, lysozyme-positive mucus metaplasia in crypts (LPMMC) replacing Paneth cells was found in 71.5% in CAD, in 96.4% in SVA/TVA, and in 2 cases with B. In 19.3% cases with BL/SVA/TVA, LPMMC replaced all Paneth cells in all crypts in entire sections. In crypts and villi, lysozyme-positive goblet cells (LPGC) were found in 92.8%. Changes were more frequent in the duodenal bulb than in pars descendens. In normal duodenal mucosa, absorptive enterocytes and goblet cells migrate from stem cells upwards, while Paneth cells migrate downwards, towards the base of the crypts. In celiac disease stem cells seem to have been re-programmed, as the normal production of Paneth cells in the crypts was replaced by lysozyme-producing mucus cells. LPMMC and LPGC in celiac disease might mirror an antimicrobial adaptation of stem cells to signals generated by pathogenic duodenal bacteria. The molecular mechanism(s) behind the abrogation of Paneth cells in duodenal crypts and its substitution by LPMMC in celiac disease remains to be elucidated.Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 07/2011; 459(3):339-46. DOI:10.1007/s00428-011-1129-3 · 2.56 Impact Factor
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ABSTRACT: The cells that line the mucosa of the human gastrointestinal tract (GI, that is, oral cavity, oesophagus, stomach, small intestine, large intestine, and rectum) are constantly challenged by adverse micro-environmental factors, such as different pH, enzymes, and bacterial flora. With exception of the oral cavity, these microenvironments also contain remnant cocktails of secreted enzymes and bacteria from upper organs along the tract. The density of the GI bacteria varies, from 103/mL near the gastric outlet, to 1010/mL at the ileocecal valve, to 1011 to 1012/mL in the colon. The total microbial population (ca. 1014) exceeds the total number of cells in the tract. It is, therefore, remarkable that despite the prima facie inauspicious mixture of harmful secretions and bacteria, the normal GI mucosa retains a healthy state of cell renewal. To counteract the hostile microenvironment, the GI epithelia react by speeding cell exfoliation (the GI mucosa has a turnover time of two to three days), by increasing peristalsis, by eliminating bacteria through secretion of plasma cell-immunoglobulins and by increasing production of natural antibacterial compounds, such as defensin-5 and lysozyme. Only recently, lysozyme was found up-regulated in Barrett's oesophagitis, chronic gastritis, gluten-induced atrophic duodenitis (coeliac disease), collagenous colitis, lymphocytic colitis, and Crohn's colitis. This up-regulation is a response directed to the special types of bacteria recently detected in these diseases. The aim of lysozyme up-regulation is to protect individual mucosal segments to chronic inflammation. The molecular mechanisms connected to the crosstalk between the intraluminal bacterial flora and the production of lysozyme released by the GI mucosae, are discussed. Bacterial resistance continues to exhaust our supply of commercial antibiotics. The potential use of lysozyme to treat infectious diseases is receiving much attention.Pathogens 03/2014; 3(1):73-92. DOI:10.3390/pathogens3010073