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At least 19 recordsLinked to original sources
PubMed1997

Characterization of a 180-kDa intestinal epithelial cell membrane glycoprotein, gp180. A candidate molecule mediating t cell-epithelial cell interactions.

Previous studies have shown that normal human intestinal epithelial cells stimulate CD8(+) suppressor T cell proliferation in an allogeneic mixed epithelial/T cell co-culture system, which is neither restricted by class I or class II major histocompatibility complex antigens nor by any soluble factors from epithelial cells. Two epithelial specific monoclonal antibodies (mAb), mAb B9 and mAb L12, are potent inhibitors of this mixed epithelial/T cell reaction but not of conventional mixed lymphocyte reactions. While phenotypically distinct by tissue staining, both mAbs recognize a 180-kDa epithelial membrane glycoprotein (gp180). Further characterization of gp180 revealed the following. 1) The protein migrated between 150 and 180 kDa in SDS-polyacrylamide gel electrophoresis and could be resolved by Western blot using mAb B9 or mAb L12. 2) The molecule has two forms, an apically sorted glycosylphosphatidylinositol-anchored form and a basolateral transmembrane form. 3) gp180 is heavily N-glycosylated, since N-glycanase treatment results in a >50% reduction in size. 4) Purified gp180 can bind to peripheral blood T cells and activate p56(lck). 5) gp180 can activate p56(lck) in 3G8 (a murine T cell hybridoma transfected with human CD8alpha cDNA) but not in 3G4 (CD4 transfectant), suggesting that gp180 binds to CD8. Thus, gp180 appears to be a novel regulator of mucosal immune responses.

Animals↗
PubMed1996

Nitric oxide donors induce apoptosis in glomerular mesangial cells, epithelial cells and endothelial cells.

Renal mesangial cells exposed to inflammatory cytokines produce high concentrations of nitric oxide (NO) which may exert cytotoxic actions. We report here that glomerular mesangial cells, endothelial cells and epithelial cells in culture are themselves targets for NO and undergo apoptotic cell death upon exposure to high concentrations of NO. NO generated from different NO-releasing compounds as well as NO-saturated solution induce apoptosis in all three cell types as demonstrated by internucleosomal DNA fragmentation, an enrichment of cytosolic DNA/histone complexes, an increasing number of cellular 3'-OH-fragmented DNA ends and typical nuclear chromatin condensation. Induction of apoptosis was found to be dependent on protein synthesis and is preceded by expression of the tumour suppressor gene product p53 in mesangial cells. Induction of inducible NO synthase in mesangial cells by interleukin-1 beta leads to excessive formation of NO by the cells as measured by nitrite production. However, there was no evidence for apoptotic changes in mesangial cells triggered by endogenously produced NO. Co-cultures of glomerular endothelial or epithelial cells with interleukin-1 beta-activated mesangial cells expressing inducible NO synthase do not show apoptotic alterations in endothelial or epithelial cells. Moreover, preincubation of mesangial cells with interleukin-1 beta protects the cells from apoptosis induced by subsequent addition of exogenous NO thus suggesting that interleukin-1 beta not only triggers the expression of inducible NO synthase and massive NO formation but simultaneously stimulates a protecting principle in the cells. In summary, these results suggest that exogenous NO can induce apoptosis in all three types of intrinsic glomerular cells. However, whether endogenously produced NO can fulfil this function critically depends on a balance between a yet to be defined protective mechanism and inducible NO synthase expression in mesangial cells in response to interleukin-1 beta and eventually other inflammatory cytokines.

Animals↗
PubMed2001

P2Y receptors of MDCK cells: epithelial cell regulation by extracellular nucleotides.

1. Madin-Darby canine kidney (MDCK) cells, a well- differentiated renal epithelial cell line derived from distal tubule/collecting duct, respond to extracellular nucleotides by altering ion flux and the production of arachidonic acid-derived products, in particular prostaglandin E2 (PGE2). Our work has defined the receptors and signalling events involved in such responses. 2. We have found evidence for expression of at least three P2Y receptor subtypes (P2Y1, P2Y2 and P2Y11) in MDCK-D1 cells, a subclone from parental MDCK. 3. These receptors appear to couple to increases in calcium and protein kinase C activity, probably via a Gq/G11-mediated activation of phospholipase C. 4. In addition, P2Y receptor activation can promote a prominent increase in cAMP. This includes both a P2Y2 receptor-mediated cyclo-oxygenase (COX)-dependent component and another COX-independent component mediated by other P2Y receptors. 5. We have documented that changing media in which cells are grown releases ATP and, in turn, activates P2Y receptors. Such release of ATP contributes in a major way to basal cAMP levels in these cells. 6. The data indicate that MDCK cells are a useful model to define the regulation of epithelial cells by extracellular nucleotides. Of particular note, spontaneous or stretch-induced release of ATP and subsequent activation of one or more P2Y receptors contributes to establishing the basal activity of signalling pathways.

Adenosine Triphosphate↗
PubMed2000

Kidney proximal tubule cells: epithelial cells without EGTA-extractable annexins?

The expression and the subcellular localizations of annexins I, II, IV, VI, and XIII in renal epithelial cells were investigated, using immunological techniques with specific monoclonal antibodies. Upon performing Western blotting experiments, no annexins VI and XIII were detected in kidney, whereas annexins I, II, and IV were. Immunofluorescence labelling procedure performed on thin frozen renal sections showed the presence of these three annexins along the plasma membrane of the collecting duct cells with a restricted expression of annexin I at principal cells. Annexin I was also found present in some glomerular cells. None of these annexins, however, were detected in the proximal tubular cells upon performing immunofluorescence labelling and electrophoretic analysis on an EGTA (ethylenebis(oxyethylenenitrilo)tetraacetic acid)-extractable annexin fraction prepared from freshly isolated cells. This is the first time a mammalian epithelial cell has been found to express non-typical annexin (at least partly solubilized with EGTA). However, when these cells were grown in primary culture, they were found to express annexins I, II, IV, and V. As well as being located along the basolateral membrane, annexins I and II are also present on vesicles, which suggests that these annexins may be involved in vesicular traffic under cell culture conditions.

Animals↗
PubMed1996

Cyclosporine A regulates T cell-epithelial cell adhesion by altering LFA-1 and ICAM-1 expression.

In contrast to the well characterized suppressive effect of cyclosporine A (CsA) on IL-2 gene transcription in T cells, other immunosuppressive effects of CsA have received less attention. We have examined the effect of CsA on the expression of the beta 2 integrin, LFA-1, and its counter receptor, ICAM-1, on a renal Ag-specific murine T cell clone and Ag-expressing renal tubular epithelial cells. We have found that CsA has a concentration dependent effect on the expression of both ICAM-1 mRNA and gene product on renal tubular cells. At 0.1 microgram/ml, CsA exhibits a costimulatory effect, with TNF alpha, on ICAM-1 expression. CsA at 1 to 5 micrograms/ml exhibits concentration dependent inhibition of ICAM-1 cell surface expression by the tubular cells. Although CsA does not inhibit ICAM-1 on T cells, it does inhibit surface expression of LFA-1. The concentration dependent effects of CsA on ICAM-1 expression correlate well with ICAM-1 dependent T cell adhesion to TNF alpha stimulated tubular epithelial cells. TGF-beta 1 has similar effects on ICAM-1 and LFA-1 expression as high dose CsA, but the CsA effects are not mediated through induced TGF-beta 1 expression. Our studies support the conclusion that CsA may bidirectionally alter ICAM-1 dependent cellular adhesive interactions. The inhibition of cytokine stimulated ICAM-1 expression at higher CsA concentrations would contribute to the overall immunosuppressive effect of the drug.

Animals↗
PubMed1997

Induction of aminopeptidase N/CD13 on human lymphocytes after adhesion to fibroblast-like synoviocytes, endothelial cells, epithelial cells, and monocytes/macrophages.

Aminopeptidase N (APN/CD13) is a transmembrane ectoenzyme occurring on a wide variety of cells. In contrast to monocytes and granulocytes, lymphocytes of peripheral blood do not express CD13 Ag. However, tumor-infiltrating T cells in renal cell cancer as well as synovial fluid T cells from patients suffering from various forms of arthritis can be CD13 positive. To learn more about expression of CD13 in these tissues, we cocultured lymphocytes with different adherent cell lines. CD13 expression was induced in T and B lymphocytes upon adhesion to fibroblast-like synoviocytes, HUVEC, renal tubular epithelial cells, and monocytes/macrophages but not always upon interaction with different tumor cell lines. Induction of APN was rapid, occurring as early as 1 h after coincubation. Expression persisted for >3 days and partially resisted inhibition by cycloheximide. Fixation of adherent cells with paraformaldehyde could not prevent induction of CD13 in lymphocytes. Soluble APN from human kidneys or placenta could not induce CD13 expression on lymphocytes. Induction of CD13 Ag on lymphocytes required direct cell-to-cell contact as shown in experiments using dual chambers. Lymphocytes exhibited an induction not only in CD13 protein but also in Ala-pNA-cleaving enzyme activity and in CD13 mRNA. Lymphocytic expression of CD13 represents a potentially increased cellular ability to inactivate inflammatory mediators. Furthermore, CD13 could be involved in adhesion, in lymphocytic migration, or in the Ag processing of peptides bound in the groove of MHC class II molecules.

B-Lymphocytes↗
PubMed1998

Isolation of human conjunctival mast cells and epithelial cells: tumor necrosis factor-alpha from mast cells affects intercellular adhesion molecule 1 expression on epithelial cells.

PURPOSE: To isolate and purify mast cells and epithelial cells from human cadaveric donor conjunctival tissue and to characterize interactions between these cell types in vitro. METHODS: Monodispersed cell suspensions obtained by enzymatic digestion of conjunctival tissue were applied to a single-density Percoll gradient. Epithelial cells obtained from the top layer of the gradient were cultured to confluence. Mast cells obtained from the pellet were equilibrated in culture medium and further purified using a two-step Percoll gradient. Using reverse transcription-polymerase chain reaction (RT-PCR), RNA from the purified mast cell preparation was probed for tumor necrosis factor-alpha (TNF alpha) message. Fluorescence activated cell sorting (FACS) analysis of intracellular immunostained mast cells was used to detect the TNF alpha protein. An examination for intercellular adhesion molecule 1 (ICAM-1) on epithelial cells was performed after 24-hour incubations with either recombinant TNF alpha supernatants from calcium ionophore A23187 (CaI)-stimulated mast cells or appropriate controls using FACS analysis. RESULTS: Highly purified human conjunctival mast cells and epithelial cells (each > 95%) were obtained from human cadaveric donor tissue. RT-PCR analysis of purified mast cell RNA revealed the expression of TNF alpha mRNA. An evaluation of mast cells for intracellular protein demonstrated positive staining for tryptase and TNF alpha. ICAM-1 was found on purified epithelial cells, and incubation of epithelial cell monolayers with supernatants from Cal-stimulated mast cells resulted in upregulation of this receptor. This upregulation was blocked by incubation with TNF alpha-neutralizing antibody. CONCLUSIONS: This work provides the methods for isolating and purifying mast cells and epithelial cells from human donor tissue and the opportunity for studying mechanisms of conjunctival inflammation by evaluating the interactions between these cells.

Calcimycin↗
PubMed1999

Inwardly rectifying K+ channel Kir7.1 is highly expressed in thyroid follicular cells, intestinal epithelial cells and choroid plexus epithelial cells: implication for a functional coupling with Na+,K+-ATPase.

A novel inwardly rectifying K+ channel, Kir7.1, with unique pore properties, was cloned recently. Working in the field of osmoregulation, we have also identified the same human and rat channel and found that the channel is unique not only in its pore sequence but also in its dense localization in the follicular cells of the thyroid gland. Northern blot analysis revealed that the channel message was abundantly expressed in the thyroid gland and small intestine, and moderately in the kidney, stomach, spinal cord and brain. Immunohistochemistry of the rat thyroid, intestine and choroid plexus demonstrated the expression of the channel protein in the follicular cells and epithelial cells, suggesting a role in the regulation of the ion-transporting functions of these specialized cells. The unique pore properties of Kir7.1 make it a strong candidate for the hypothetical low-conductance K+ channel that is functionally coupled with Na+,K(+)-ATPase by recycling K+. We therefore further examined the co-localization of Kir7.1 and Na+,K(+)-ATPase and found that both are localized in the basolateral membrane of the thyroid follicular cell; in the choroid plexus, which is known to be unique in having Na+,K(+)-ATPase in the apical side of the epithelial cells, Kir7.1 was found in the apical membrane, implying a close functional coupling between the channel and Na+,K(+)-ATPase.

Amino Acid Sequence↗
PubMed2002

Polarized angular dependent spectroscopy of epithelial cells and epithelial cell nuclei to determine the size scale of scattering structures.

An understanding of the relationship between tissue structures and light scattering from tissue will help facilitate the development and acceptance of noninvasive optical diagnostics including elastic scattering spectroscopy, diffuse reflectance, and optical coherence tomography. For example, a quantitative model of the structures that scatter light in epithelial cells would allow determination of what structures control the characteristics of in vivo light transport measurements and subsequently could provide a detailed relationship between cellular structures and optical measurements. We have determined the size distribution of refractive index structure variations in epithelial cells as well as in nuclei isolated from epithelial cells from measurements of the angular dependence of polarized light scattering. The quantitative size distributions we obtained for both whole cells and isolated nuclei include particles with effective radii of 2 microm to 10 nm or less and contain orders of magnitude more small particles than large particles. These results demonstrate that not only are biological cells very heterogeneous, but so are the nuclei within them. Light scattering is likely sensitive to structures smaller than those commonly investigated by standard pathology methods.

Animals↗
PubMed2000

Haemophilus influenzae stimulates ICAM-1 expression on respiratory epithelial cells.

Epithelial cells interact directly with bacteria in the environment and play a critical role in airway defense against microbial pathogens. In this study, we examined the response of respiratory epithelial cells to infection with nontypable Haemophilus influenzae. Using an in vitro cell culture model, we found that epithelial cell monolayers released significant quantities of IL-8 and expressed increased levels of ICAM-1 mRNA and surface protein in response to H. influenzae. In contrast, levels of IL-1beta, TNF-alpha, and MHC class I were not significantly affected, suggesting preferential activation of a specific subset of epithelial genes directed toward defense against bacteria. Induction of ICAM-1 required direct bacterial interaction with the epithelial cell surface and was not reproduced by purified H. influenzae lipooligosaccharide. Consistent with a functional role for this response, induction of ICAM-1 by H. influenzae mediated increased neutrophil adherence to the epithelial cell surface. Furthermore, in an in vivo murine model of airway infection with H. influenzae, increased epithelial cell ICAM-1 expression coincided with increased chemokine levels and neutrophil recruitment in the airway. These results indicate that ICAM-1 expression on human respiratory epithelial cells is induced by epithelial cell interaction with H. influenzae and suggest that an ICAM-1-dependent mechanism can mediate neutrophil adherence to these cells independent of inflammatory mediator release by other cell types. Direct induction of specific epithelial cell genes (such as ICAM-1 and IL-8) by bacterial infection may allow for rapid and efficient innate defense in the airway.

Adhesins, Bacterial↗
PubMed1993

Expression and modulation of adhesion molecules on human bronchial epithelial cells.

Epithelial damage in the airways is a feature often observed in patients with asthma and is probably caused by the interaction of epithelial cells with leukocytes. As adhesion molecules are thought to be important in this interaction, we analyzed the expression and modulation of adhesion molecules on primary cultured human bronchial epithelial cells and the bronchial epithelial cell lines BEAS-2B and NCI-H292. E-selectin, P-selectin, and VCAM-1 were absent under basal and stimulated conditions. The adhesion molecules ICAM-1 (CD54), LFA-3 (CD58), and CD44 (H-CAM) were expressed basally on primary cultured human bronchial epithelial cells and the BEAS-2B and NCI-H292 cell lines. CD44 and LFA-3 expression did not change after stimulation with IFN-gamma or TNF-alpha. In contrast, ICAM-1 expression on human bronchial epithelial cells and BEAS-2B cells could be increased by incubation with PMA, IFN-gamma, TNF-alpha, and especially with the combination of IFN-gamma and TNF-alpha. The maximal ICAM-1 expression on both epithelial cell types was obtained with the combination of TNF-alpha and IFN-gamma after 48 h of incubation. The NCI-H292 cell line was different in that it only showed increased ICAM-1 expression after stimulation with PMA and IFN-gamma and not by the combination of IFN-gamma and TNF-alpha or with TNF-alpha alone. In conclusion, the bronchial epithelial cells tested express several adhesion molecules, but only ICAM-1 expression was influenced by inflammatory cytokines.

Bronchi↗
PubMed2003

Expression and distribution of distinct variants of E-MAP-115 during proliferation and differentiation of human intestinal epithelial cells.

Epithelial cell proliferation and differentiation occur concomitant with striking remodeling of the cytoskeleton. Microtubules (MTs) play important roles in these processes, during which the MTs themselves are reorganized and stabilized by microtubule-associated proteins (MAPs). Among the proteins classified as structural MAPs, E-MAP-115 (also named ensconsin) is preferentially expressed in cells of epithelial origin. The aims of this study were, first, to determine if E-MAP-115, like other MAPs, is expressed as different isoforms during differentiation and, second, to perform a detailed analysis of the expression and distribution of any E-MAP-115 variants detected in intestinal epithelial cells during their polarization/differentiation. It was our expectation that these data would help us to develop hypotheses concerning the role of this MAP in epithelial development. We report the expression of three E-MAP-115 transcripts encoding isoforms of 115, 105, and 95 kDa; two display an expression gradient inverse to the third one as Caco-2 cells progress from proliferation through the stages of differentiation. To monitor the proteins produced from each transcript, we used purified polyclonal antibodies against synthetic peptides contained within the 115, 105, and 95 kDa isoforms to assay proliferating and differentiating CaCo-2 cells. Our results indicate that the expression and MT-binding capacity of the 115, 105, and 95 kDa isoforms vary upon proliferation/differentiation of the cells. E-MAP-115 proteins colocalize with MTs in proliferative and differentiated Caco-2 cells; in vivo, they are expressed in both crypt and villus epithelial cells where they are mainly concentrated at the apical pole of the cells.

Humans↗
PubMed1991

Morphological and immunocytochemical characterization of cultured rat incisor cervical epithelial cells.

Epithelial cells from the cervical loop of the rat incisor were isolated by co-culture of apical explants with growth-arrested 3T3 fibroblasts. The epithelial phenotype of the expanding outgrowths was confirmed 10 days after the seeding of the explants by phase-contrast microscopy and immunocytochemical identification of cytokeratins. After 3 weeks in culture, the epithelial cells covered the entire surface of the coverslips and were then passaged. Subcultures gave rise to a confluent sheet within 10-12 days. Light and electron microscopy showed that confluent cervical epithelial cells generally reconstituted a bi-layered structure similar to Hertwig's epithelial sheath. Epithelial cells from the rat palate, cultured and subcultured according to the same procedure, organized themselves in 5-6 cell layers, the upper cells having generally a squamous morphology. Synthesis of extracellular matrix molecules by rat incisor cervical epithelial cells was studied with specific antibodies. These cells failed to produce type I collagen, but synthesized all the major basement membrane components (type IV collagen, laminin, heparan sulphate proteoglycan and fibronectin). These observations suggest that the culture conditions allowed the reconstitution of a typical Hertwig's epithelial sheath by rat incisor cervical epithelial cells.

Animals↗
PubMed2005

Mutations of Epstein-Barr virus gH that are differentially able to support fusion with B cells or epithelial cells.

The core fusion machinery of all herpesviruses consists of three conserved glycoproteins, gB and gHgL, suggesting a common mechanism for virus cell fusion, but fusion of Epstein-Barr virus (EBV) with B cells and epithelial cells is initiated differently. Fusion with B cells requires a fourth protein, gp42, which complexes with gHgL and interacts with HLA class II, the B-cell coreceptor. Fusion with an epithelial cell does not require gp42 but requires interaction of gHgL with a novel epithelial cell coreceptor. Epithelial cell fusion can be inhibited by gp42 binding to gHgL and by antibodies to gH that fail to block B-cell fusion. This suggests that regions of gHgL initiating fusion with each cell are separable from each other and from regions involved in fusion itself. To address this possibility we mapped the region of gH recognized by a monoclonal antibody to gH that blocks EBV fusion with epithelial cells but not B cells by making a series of chimeras with the gH homolog of rhesus lymphocryptovirus. Proteins with mutations engineered within this region included those that preferentially mediate fusion with B cells, those that preferentially mediate fusion with epithelial cells, and those that mediate fusion with neither cell type. These results support the hypothesis that the core fusion function of gH is the same for B cells and epithelial cells and that it differs only in the way in which it is triggered into a functionally active state.

Amino Acid Sequence↗
PubMed1991

Endocytotic activity of the free floating cells and epithelial cells in the endolymphatic sac: an electron microscopic study.

The fine structure and its functional properties of both free floating cells and epithelial cells in the endolymphatic sac after injections of India ink particles or polystyrene latex beads, 0.24 micron in diameter, into the endolymphatic space, were studied using light and electron microscopy. Twenty-four to 48 hours after injections, these foreign materials had accumulated in the lumen of the endolymphatic sac and a large number of them were ingested into free floating cells, most of which appear to be macrophages. Granular leucocytes taking up the foreign materials into the cytoplasm were also recognized in the sac lumen. A few of these leucocytes passed through the epithelium and migrated to the subepithelial connective tissue, while the others were degenerated and phagocytosed by the free floating cells in the lumen of the sac. In addition to the free floating cells, ink particles, latex beads, and degenerated leucocytes were endocytosed into some of the epithelial cells. As we reported previously, the epithelial cells were clearly classified into two types; type-1 epithelial cells (cytoorganelle-rich cells) and type-2 epithelial cells (filament-rich cells). The foreign materials and degenerated cells were taken up mainly into the type-1 epithelial cells, while the type-2 epithelial cells did not show so marked endocytotic activity in comparison with the type-1 epithelial cells. Thus, it becomes clear that the endolymphatic sac plays an important role in the endocytotic activity for foreign materials and waste products, and both the free floating cells and the type-1 epithelial cells of the sac have strong endocytotic activity.

Animals↗
PubMed2006

Membrane-bound eotaxin-3 mediates eosinophil transepithelial migration in IL-4-stimulated epithelial cells.

Epithelial cells play an important role in orchestrating mucosal immune responses. In allergic-type inflammation, epithelial cells control the recruitment of eosinophils into the mucosa. Th2-type cytokine-driven release of eosinophil-active chemokines from epithelial cells directs eosinophil migration into the mucosal epithelium. CCR3, the main eosinophil chemokine receptor, regulates this process; however, the respective contribution of individual CCR3 ligands in eosinophil transepithelial migration is less well understood. Using an in vitro transepithelial chemotaxis system, we found that eotaxin-3 produced by IL-4-stimulated airway epithelial cells and CCR3 on eosinophils exclusively mediate eosinophil transepithelial migration. Eotaxin-3 protein levels were also increased in the nasal mucosal epithelium recovered from allergic patients as compared to non-allergic patients. Surprisingly, eotaxin-3 in IL-4-stimulated airway epithelial cells was predominantly cell surface bound, and the cell surface form was critical for eosinophil transepithelial migration. Eotaxin-3 cell surface association was partially glycosaminoglycan (GAG) dependent, but was completely protein dependent, suggesting that eotaxin-3 associates with both GAG and cell surface proteins. We thus provide evidence that cell surface-associated eotaxin-3 is the critical IL-4-dependent chemotactic signal mediating eosinophil transepithelial migration in the setting of allergic inflammation.

Blotting, Northern↗
PubMed1998

Phosphodiesterase expression in human epithelial cells.

Epithelial cells play a critical role in airway inflammation and have the capacity to produce many inflammatory mediators, including bioactive lipids and proinflammatory cytokines. Intracellular levels of cAMP and cGMP are important in the control of inflammatory cell function. These cyclic nucleotides are inactivated via a family of phosphodiesterase (PDE) enzymes, providing a possible site for drug intervention in chronic inflammatory conditions. We studied the expression of PDE activity in an epithelial cell line (A549) and in primary human airway epithelial cells (HAECs). We measured PDE function using specific inhibitors to identify the PDE families present and used RT-PCR to elucidate the expression of PDE isogenes. Both A549 cells and HAECs predominantly expressed PDE4 activity, with lesser PDE1, PDE3, and PDE5 activity. RT-PCR identified HSPDE4A5 and HSPDE4D3 together with HSPDE7. Inhibition of PDE4 and PDE3 reduced secretion by these cells. Epithelial PDE may be an important target for PDE4 inhibitors in the development of the control of asthmatic inflammation, particularly when delivered via the inhaled route.

1-Methyl-3-isobutylxanthine↗