No abstract

No abstract

Colonocyte exfoliation in the human colon constitutes a unique mechanism of cell population control that can undergo significant changes under different physiological and pathological conditions. Being closely related to the apoptosis and anoikis, cell exfoliation from colonic epithelium appears to be a relatively rare event in normal conditions, but its rate dramatically increases in neoplasia, when cell removal by apoptosis in situ does not function properly. Several studies show that significant numbers of exfoliated colonocytes are not lost in the faecal contents of the gut, but retained in the mucocellular layer overlying colonic mucosa. Recent observations allow hypothesizing that the mucocellular layer containing exfoliated colonocytes may gradually migrate distally, eventually leading to the accumulation of the cells exfoliated from malignant colorectal tumours on the surface of the rectal mucosa. Implications of exfoliated colonocyte analysis to colorectal cancer screening and early diagnosis are discussed. ' 2007 Wiley-Liss, Inc.Key words: colonic epithelium; cell exfoliation; mucocellular layer; neoplastic growth; colorectal cancer screening Intense investigation of epithelial cell proliferation in the mammalian intestinal mucosa has resulted in a significant progress in understanding regulatory mechanisms governing cell dynamics in this rapidly self-renewing cell population. This understanding greatly assisted in developing theoretical models of human colorectal carcinogenesis addressing both its molecular mechanisms [1][2][3][4] and sequences of events in tumour morphogenesis. [5][6][7][8][9][10] As numerous studies in this area were devoted to the investigation of colonocyte proliferation and differentiation, relatively little remained known about the final natural destiny of these cells. Obligatory exfoliation of terminally differentiated colonocytes was traditionally believed to be the predominant way of cell loss in colonic epithelium, 11 but this popular notion remained essentially hypothetical in the absence of convincing firm evidence. Given that it has become generally admitted that exfoliated colonocyte analysis may open new approaches to colorectal cancer screening and early diagnosis, detailed knowledge and better understanding of the exfoliation of colonic epithelium and its changes in neoplasia is of high practical relevance. The present brief review addresses this surprisingly obscure area with the purpose of clarifying a few points still provoking controversy and confusion. Perspectives of using the phenomenon of colonic cell exfoliation for screening and diagnosis of colorectal cancer and related diseases are then reevaluated in view of recent advances in the field.Cell exfoliation in the colonic epithelium: Its role in normal physiological conditions and neoplasia Colonic epithelium is known to be one of the most dynamic cell populations of the human organism. 4,8,11,12 Meticulous investigation of the well-structured organisation of the colonic mucosa allowed constructing a detaile...

Eosinophils are currently regarded as versatile mobile cells controlling and regulating multiple biological pathways and responses in health and disease. These cells store in their specific granules numerous biologically active substances (cytotoxic cationic proteins, cytokines, growth factors, chemokines, enzymes) ready for rapid release. The human gut is the main destination of eosinophils that are produced and matured in the bone marrow and then transferred to target tissues through the circulation. In health the most important functions of gut-residing eosinophils comprise their participation in the maintenance of the protective mucosal barrier and interactions with other immune cells in providing immunity to microbiota of the gut lumen. Eosinophils are closely involved in the development of inflammatory bowel disease (IBD), when their cytotoxic granule proteins cause damage to host tissues. However, their roles in Crohn’s disease and ulcerative colitis appear to follow different immune response patterns. Eosinophils in IBD are especially important in altering the structure and protective functions of the mucosal barrier and modulating massive neutrophil influx to the lamina propria followed by transepithelial migration to colorectal mucus. IBD-associated inflammatory process involving eosinophils then appears to expand to the mucus overlaying the internal gut surface. The author hypothesises that immune responses within colorectal mucus as well as ETosis exerted by both neutrophils and eosinophils on the both sides of the colonic epithelial barrier act as additional pathogenetic factors in IBD. Literature analysis also shows an association between elevated eosinophil levels and better colorectal cancer (CRC) prognosis, but mechanisms behind this effect remain to be elucidated. In conclusion, the author emphasises the importance of investigating colorectal mucus in IBD and CRC patients as a previously unexplored milieu of disease-related inflammatory responses.