Extrusion of colonic epithelial cells in vitro

Baron, David; Miller, Donald H.

doi:10.1002/jemt.1060160104

Cited by 14 publications

(11 citation statements)

References 18 publications

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“…In support of our findings, it has recently been shown in the mouse jejunum epithelium that the process of cell shedding requires redistribution of ZO-1 prior to cell extrusion and that shed epithelial cells undergo nuclear chromatin condensation, a hallmark of apoptosis [40]. This study and others suggest that ZO-1 rearranges beneath dividing and shedding cells to maintain epithelial barrier function by connecting neighboring cells surrounding an extruding cell [41], [42], [43], [44]. Thus, loss of ZO-1 expression via down-regulation of myoferlin expression may be an active participant in catalyzing cell extrusion.…”

Section: Discussionsupporting

confidence: 91%

Expression of Myoferlin in Human Airway Epithelium and Its Role in Cell Adhesion and Zonula Occludens-1 Expression

et al. 2012

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BackgroundNormal airway epithelial barrier function is maintained by cell-cell contacts which require the translocation of adhesion proteins at the cell surface, through membrane vesicle trafficking and fusion events. Myoferlin and dysferlin, members of the multiple-C2-domain Ferlin superfamily, have been implicated in membrane fusion processes through the induction of membrane curvature. The objectives of this study were to examine the expression of dysferlin and myoferlin within the human airway and determine the roles of these proteins in airway epithelial homeostasis.MethodsThe expression of dysferlin and myoferlin were evaluated in normal human airway sections by immunohistochemistry, and primary human airway epithelial cells and fibroblasts by immuno blot. Localization of dysferlin and myoferlin in epithelial cells were determined using confocal microscopy. Functional outcomes analyzed included cell adhesion, protein expression, and cell detachment following dysferlin and myoferlin siRNA knock-down, using the human bronchial epithelial cell line, 16HBE.ResultsPrimary human airway epithelial cells express both dysferlin and myoferlin whereas fibroblasts isolated from bronchi and the parenchyma only express myoferlin. Expression of dysferlin and myoferlin was further localized within the Golgi, cell cytoplasm and plasma membrane of 16HBE cells using confocal micrscopy. Treatment of 16HBE cells with myoferlin siRNA, but not dysferlin siRNA, resulted in a rounded cell morphology and loss of cell adhesion. This cell shedding following myoferlin knockdown was associated with decreased expression of tight junction molecule, zonula occludens-1 (ZO-1) and increased number of cells positive for apoptotic markers Annexin V and propidium iodide. Cell shedding was not associated with release of the innate inflammatory cytokines IL-6 and IL-8.Conclusions/SignificanceThis study demonstrates the heterogeneous expression of myoferlin within epithelial cells and fibroblasts of the respiratory airway. The effect of myoferlin on the expression of ZO-1 in airway epithelial cells indicates its role in membrane fusion events that regulate cell detachment and apoptosis within the airway epithelium.

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Section: Discussionsupporting

confidence: 91%

Expression of Myoferlin in Human Airway Epithelium and Its Role in Cell Adhesion and Zonula Occludens-1 Expression

et al. 2012

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“…This process occurs when neighboring cells contract to push a dying cell out of the monolayer and is characterized by reorganization of adherens and tight junctions to maintain the integrity of the epithelial monolayer (19)(20)(21)(22). Here, we observed similar actin contractile rings and tight junction "rosettes" at the base of extruding Salmonella-infected cells (Fig.…”

Section: Resultssupporting

confidence: 56%

Dissemination of invasiveSalmonellavia bacterial-induced extrusion of mucosal epithelia

Knodler

Vallance

Celli

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

373

536

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Salmonella enterica is an intracellular bacterial pathogen that resides and proliferates within a membrane-bound vacuole in epithelial cells of the gut and gallbladder. Although essential to disease, how Salmonella escapes from its intracellular niche and spreads to secondary cells within the same host, or to a new host, is not known. Here, we demonstrate that a subpopulation of Salmonella hyperreplicating in the cytosol of epithelial cells serves as a reservoir for dissemination. These bacteria are transcriptionally distinct from intravacuolar Salmonella. They are induced for the invasion-associated type III secretion system and possess flagella; hence, they are primed for invasion. Epithelial cells laden with these cytosolic bacteria are extruded out of the monolayer, releasing invasion-primed and -competent Salmonella into the lumen. This extrusion mechanism is morphologically similar to the process of cell shedding required for turnover of the intestinal epithelium. In contrast to the homeostatic mechanism, however, bacterial-induced extrusion is accompanied by an inflammatory cell death characterized by caspase-1 activation and the apical release of IL-18, an important cytokine regulator of gut inflammation. Although epithelial extrusion is obviously beneficial to Salmonella for completion of its life cycle, it also provides a mechanistic explanation for the mucosal inflammation that is triggered during Salmonella infection of the gastrointestinal and biliary tracts.

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“…In washouts from these species, nucleated cell elements are found. A similar mechanism of whole cell extrusion is seen in vitro in rat colon (Baron and Miller 1990).…”

Section: Introductionsupporting

confidence: 58%

Further evidence of species variation in mechanisms of epithelial cell loss in mammalian small intestine: ultrastructural studies on the reindeer ( Rangifer tarandus ) and seal ( Phoca groenlandica )

Myklebust

Mayhew

1998

Cell and Tissue Research

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Ultrastructural studies were conducted on mechanisms of epithelial cell loss in the small intestine of seal and reindeer. Mechanisms maintaining epithelial integrity were distinguished from those that did not and the non-epithelial cell types involved were identified. Three types of cell extrusion were noted. In two, tight junctional integrity was preserved and anucleate apical cell fragments (rather than complete cells) were lost into the lumen. In reindeer (type 1), this involved creating large intercellular spaces extending from the preserved apical cap to the lamina propria and containing enterocyte debris probably phagocytosed by subepithelial macrophages. A variant of this process (type 2) involved the gradual shrinkage of individual cells, which became more electron-dense, and the in situ degeneration of their nucleated subapical portions. Degenerated cell fragments and membrane whorls were confined to narrow intercellular spaces between approximating adjacent healthy enterocytes. The mechanism of removal of these fragments was unclear. In both cases, the proximity of intraepithelial lymphocytes suggested that they were involved in cell targetting and killing. Evidence of apoptotic nuclei was not found but nucleated cell fragments could have been washed out of the lumen during tissue preparation. Type 2 cell loss was seen in both species, as was another mechanism (type 3) reminiscent of necrosis. In contrast to other mechanisms, this was accompanied by breaks in epithelial continuity following gradual loss of cell electron density and total or subtotal degradation of organelles and membranes. In seal, this terminated in the loss of an abnormal cell apex and exposure of the contents of the cell remnant to the lumen. In reindeer, all the cell remnants may have been extruded before total membrane degeneration but, in both species, the otherwise tight epithelial barrier was clearly breached. Again, intraepithelial lymphocytes were associated with sites of necrosis. These findings provide evidence for further species differences in mechanisms of epithelial cell extrusion and suggest that necrotic cell loss may be more common than previously admitted.

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Extrusion of colonic epithelial cells in vitro

Cited by 14 publications

References 18 publications

Expression of Myoferlin in Human Airway Epithelium and Its Role in Cell Adhesion and Zonula Occludens-1 Expression

Expression of Myoferlin in Human Airway Epithelium and Its Role in Cell Adhesion and Zonula Occludens-1 Expression

Dissemination of invasiveSalmonellavia bacterial-induced extrusion of mucosal epithelia

Further evidence of species variation in mechanisms of epithelial cell loss in mammalian small intestine: ultrastructural studies on the reindeer ( Rangifer tarandus ) and seal ( Phoca groenlandica )

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