MUCI, glycans and the cell-surface barrier to embryo implantation

As it approaches the maternal surface, the attaching embryo encounters the epithelial glycocalyx, which contains the mucin, MUC1. A high density of MUC1 at the cell surface can inhibit cell adhesion. This raises the possibility of the existence of a uterine barrier to implantation that might allow maternal rejection of poorer quality embryos. To investigate the mechanism of implantation, human embryos were incubated with endometrial epithelial monolayers. Hatched blastocysts were found to attach readily to the epithelial surface. MUC1 was lost from epithelial cells beneath and near to the attached embryo, while normal expression persisted in neighbouring cells.

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Redistribution and dysfunction of integrins in cultured renal epithelial cells exposed to oxidative stress

AJP Renal Physiology ◽

10.1152/ajprenal.1993.264.1.f149 ◽

1993 ◽

Vol 264 (1) ◽

pp. F149-F157 ◽

Cited By ~ 14

Author(s):

J. Gailit ◽

D. Colflesh ◽

I. Rabiner ◽

J. Simone ◽

M. S. Goligorsky

Keyword(s):

Oxidative Stress ◽

Cell Adhesion ◽

Epithelial Cell ◽

Epithelial Cells ◽

Cell Surface ◽

Apical Cell ◽

Flow Cytometric Analysis ◽

Adhesion Properties ◽

Renal Tubular Cells ◽

Renal Tubular

Tubular obstruction by detached renal tubular epithelial cells is a major cause of oliguria in acute renal failure. Viable renal tubular cells can be recovered from urine of patients with acute tubular necrosis, suggesting a possible defect in cell adhesion to the basement membrane. To study this process of epithelial cell desquamation in vitro, we investigated the effect of nonlethal oxidative stress on the integrin adhesion receptors of the primate kidney epithelial cell line BS-C-1. Morphological and functional studies of cell adhesion properties included the following: interference reflection microscopy, intravital confocal microscopy and immunocytochemistry, flow cytometric analysis of integrin receptor abundance, and cell-matrix attachment assay. High levels of the integrin subunits alpha 3, alpha v, and beta 1 were detected on the cell surface by fluorescence-activated cell sorting (FACS) analysis, as well as lower levels of alpha 1, alpha 2, alpha 4, alpha 5, alpha 6, and beta 3. Exposure of BS-C-1 cells to nonlethal oxidative stress resulted in the disruption of focal contacts, disappearance of talin from the basal cell surface, and in the redistribution of integrin alpha 3-subunits from predominantly basal location to the apical cell surface. As measured in a quantitative cell attachment assay, oxidative stress decreased BS-C-1 cell adhesion to type IV collagen, laminin, fibronectin, and vitronectin. Defective adhesion was not associated with a loss of alpha 3-, alpha 4-, or alpha v-integrin subunits from the cell surface.(ABSTRACT TRUNCATED AT 250 WORDS)

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Regulation of epithelial and lymphocyte cell adhesion by adenosine deaminase–CD26 interaction

Biochemical Journal ◽

10.1042/bj3610203 ◽

2002 ◽

Vol 361 (2) ◽

pp. 203-209 ◽

Cited By ~ 4

Author(s):

Silvia GINÉS ◽

Marta MARIÑO ◽

Josefa MALLOL ◽

Enric I. CANELA ◽

Chikao MORIMOTO ◽

...

Keyword(s):

T Cells ◽

Cell Adhesion ◽

T Cell ◽

B Cells ◽

Epithelial Cell ◽

Epithelial Cells ◽

Cell Surface ◽

Adenosine Deaminase ◽

Cell To Cell Adhesion ◽

Lymphocyte Cell

The extra-enzymic function of cell-surface adenosine deaminase (ADA), an enzyme mainly localized in the cytosol but also found on the cell surface of monocytes, B cells and T cells, has lately been the subject of numerous studies. Cell-surface ADA is able to transduce co-stimulatory signals in T cells via its interaction with CD26, an integral membrane protein that acts as ADA-binding protein. The aim of the present study was to explore whether ADA—CD26 interaction plays a role in the adhesion of lymphocyte cells to human epithelial cells. To meet this aim, different lymphocyte cell lines (Jurkat and CEM T) expressing endogenous, or overexpressing human, CD26 protein were tested in adhesion assays to monolayers of colon adenocarcinoma human epithelial cells, Caco-2, which express high levels of cell-surface ADA. Interestingly, the adhesion of Jurkat and CEM T cells to a monolayer of Caco-2 cells was greatly dependent on CD26. An increase by 50% in the cell-to-cell adhesion was found in cells containing higher levels of CD26. Incubation with an anti-CD26 antibody raised against the ADA-binding site or with exogenous ADA resulted in a significant reduction (50–70%) of T-cell adhesion to monolayers of epithelial cells. The role of ADA—CD26 interaction in the lymphocyte—epithelial cell adhesion appears to be mediated by CD26 molecules that are not interacting with endogenous ADA (ADA-free CD26), since SKW6.4 (B cells) that express more cell-surface ADA showed lower adhesion than T cells. Adhesion stimulated by CD26 and ADA is mediated by T cell lymphocyte function-associated antigen. A role for ADA—CD26 interaction in cell-to-cell adhesion was confirmed further in integrin activation assays. FACS analysis revealed a higher expression of activated integrins on T cell lines in the presence of increasing amounts of exogenous ADA. Taken together, these results suggest that the ADA—CD26 interaction on the cell surface has a role in lymphocyte—epithelial cell adhesion.

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MUC1, glycans and the cell surface barrier to embryo implantation in human

Biochemical Society Transactions ◽

10.1042/bst029a011b ◽

2001 ◽

Vol 29 (1) ◽

pp. A11-A11

Author(s):

J. D. Aplin

Keyword(s):

Cell Surface ◽

Embryo Implantation ◽

Surface Barrier

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Dual trafficking of Slit3 to mitochondria and cell surface demonstrates novel localization for Slit protein

AJP Cell Physiology ◽

10.1152/ajpcell.2001.281.2.c486 ◽

2001 ◽

Vol 281 (2) ◽

pp. C486-C495 ◽

Cited By ~ 14

Author(s):

Melissa H. Little ◽

Lorine Wilkinson ◽

Darren L. Brown ◽

Michael Piper ◽

Toshiya Yamada ◽

...

Keyword(s):

Epithelial Cells ◽

Cell Surface ◽

Fluorescent Protein ◽

Protein Localization ◽

Proteolytic Processing ◽

Proximal Tubule Cells ◽

Epithelial Monolayers ◽

Vertebrate Orthologs ◽

Localization Signal ◽

Green Fluorescent

Drosophila slit is a secreted protein involved in midline patterning. Three vertebrate orthologs of the fly slit gene, Slit1, 2, and 3, have been isolated. Each displays overlapping, but distinct, patterns of expression in the developing vertebrate central nervous system, implying conservation of function. However, vertebrate Slit genes are also expressed in nonneuronal tissues where their cellular locations and functions are unknown. In this study, we characterized the cellular distribution and processing of mammalian Slit3 gene product, the least evolutionarily conserved of the vertebrate Slit genes, in kidney epithelial cells, using both cellular fractionation and immunolabeling. Slit3, but not Slit2, was predominantly localized within the mitochondria. This localization was confirmed using immunoelectron microscopy in cell lines and in mouse kidney proximal tubule cells. In confluent epithelial monolayers, Slit3 was also transported to the cell surface. However, we found no evidence of Slit3 proteolytic processing similar to that seen for Slit2. We demonstrated that Slit3 contains an NH2-terminal mitochondrial localization signal that can direct a reporter green fluorescent protein to the mitochondria. The equivalent region from Slit1 cannot elicit mitochondrial targeting. We conclude that Slit3 protein is targeted to and localized at two distinct sites within epithelial cells: the mitochondria, and then, in more confluent cells, the cell surface. Targeting to both locations is driven by specific NH2-terminal sequences. This is the first examination of Slit protein localization in nonneuronal cells, and this study implies that Slit3 has potentially unique functions not shared by other Slit proteins.

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Antiadhesive Role of Apical Decay-accelerating Factor (CD55) in Human Neutrophil Transmigration across Mucosal Epithelia

Journal of Experimental Medicine ◽

10.1084/jem.20030380 ◽

2003 ◽

Vol 198 (7) ◽

pp. 999-1010 ◽

Cited By ~ 60

Author(s):

Donald W. Lawrence ◽

Walter J. Bruyninckx ◽

Nancy A. Louis ◽

Douglas M. Lublin ◽

Gregory L. Stahl ◽

...

Keyword(s):

Cell Surface ◽

Plasma Membranes ◽

Apical Cell ◽

Neutrophil Migration ◽

Surface Proteins ◽

Epithelial Surface ◽

Decay Accelerating Factor ◽

Apical Cell Membrane ◽

Epithelial Monolayers ◽

Epithelial Cell Surface

Neutrophil migration across mucosal epithelium during inflammatory episodes involves the precise orchestration of a number a cell surface molecules and signaling pathways. After successful migration to the apical epithelial surface, apically localized epithelial proteins may serve to retain PMN at the lumenal surface. At present, identification of apical epithelial ligands and their PMN counter-receptors remain elusive. Therefore, to define the existence of apical epithelial cell surface proteins involved in PMN–epithelial interactions, we screened a panel of antibodies directed against epithelial plasma membranes. This strategy identified one antibody (OE-1) that both localized to the apical cell membrane and significantly inhibited PMN transmigration across epithelial monolayers. Microsequence analysis revealed that OE-1 recognized human decay-accelerating factor (DAF, CD55). DAF is a highly glycosylated, 70–80-kD, glycosyl-phosphatidyinositol–linked protein that functions predominantly as an inhibitor of autologous complement lysis. DAF suppression experiments using antisense oligonucleotides or RNA interference revealed that DAF may function as an antiadhesive molecule promoting the release of PMN from the lumenal surface after transmigration. Similarly, peptides corresponding to the antigen recognition domain of OE-1 resulted in accumulation of PMN on the apical epithelial surface. The elucidation of DAF as an apical epithelial ligand for PMN provides a target for novel anti-inflammatory therapies directed at quelling unwanted inflammatory episodes.

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Interleukin-11 and Leukemia Inhibitory Factor Regulate the Adhesion of Endometrial Epithelial Cells: Implications in Fertility Regulation

Endocrinology ◽

10.1210/en.2008-1538 ◽

2009 ◽

Vol 150 (6) ◽

pp. 2915-2923 ◽

Cited By ~ 73

Author(s):

M. Marwood ◽

K. Visser ◽

L. A. Salamonsen ◽

E. Dimitriadis

Keyword(s):

Cell Adhesion ◽

Epithelial Cell ◽

Epithelial Cells ◽

Leukemia Inhibitory Factor ◽

Embryo Implantation ◽

Neutralizing Antibody ◽

Collagen Iv ◽

Inhibitory Factor ◽

Endometrial Epithelial Cell ◽

Endometrial Epithelial Cells

Embryo implantation requires the closely harmonized processes of apposition, attachment, and adhesion of the conceptus to the maternal endometrial epithelium. IL-11 and leukemia inhibitory factor (LIF), two IL-6 family cytokines, are produced by the endometrium and are absolutely required for implantation in mice. We examined the effect of IL-11 and LIF on human endometrial epithelial cell adhesion. Both cytokines increased adhesion of primary human endometrial epithelial cells to fibronectin and collagen IV. IL-11 stimulated, whereas LIF had no effect on the adhesion of trophoblast to endometrial epithelial cells. Focused oligogene arrays were used to identify extracellular matrix and adhesion molecules mRNAs regulated by endometrial epithelial cells. We demonstrated by real-time RT-PCR and antibody arrays that both cytokines increased integrin-α2 mRNA and protein by endometrial epithelial cells. Signal transducers and activators of transcription (STAT)-3 inhibition reduced IL-11- and LIF-mediated epithelial cell adhesion to fibronectin, suggesting both cytokines regulated adhesion via phosphorylation of STAT3. Addition of either IL-11 neutralizing antibody and IL-11 or LIF and LIF antagonist to endometrial epithelial cells abolished cytokine induced phosphorylated STAT3. LIF but not IL-11 induced adhesion to collagen IV was reduced by an integrin-α2β1 neutralizing antibody. This study demonstrated that IL-11 and LIF regulated endometrial epithelial cell adhesion, suggesting that targeting IL-11 and LIF may be useful in regulating fertility by either enhancing or blocking implantation.

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Adherence of Candida albicans to buccal and vaginal epithelial cells: ultrastructural observations

Canadian Journal of Microbiology ◽

10.1139/m84-156 ◽

1984 ◽

Vol 30 (8) ◽

pp. 1001-1007 ◽

Cited By ~ 25

Author(s):

Richard A. Calderone ◽

Nurith Lehrer ◽

Esther Segal

Keyword(s):

Candida Albicans ◽

Epithelial Cell ◽

Epithelial Cells ◽

Cell Surface ◽

Host Cells ◽

Yeast Cells ◽

Dense Matrix ◽

Epithelial Surface ◽

Vaginal Epithelial Cells ◽

Epithelial Cell Surface

The adherence of Candida albicans to human buccal and vaginal epithelial cells was studied by transmission electron microscopy. Adherence to epithelial cells was confirmed by both a radiometric assay as well as direct microscopic examination of stained cell preparations. Ultramicroscopic preparations revealed that yeast cells were closely appressed to epithelial cell surfaces and were often partially enclosed within phagocyticlike invaginations of the epithelial cells. A murine model of vaginitis caused by C. albicans was also used to study adherence to epithelial cells and to follow the course of colonization. Ultramicroscopic preparations of murine vaginal tissue revealed that within 2 h postinfection, yeast cells could be seen adhering to epithelial cells. At 6 h postinfection, hyphae and yeast cells were not only found on the epithelial cell surface but also within the submucosal tissue. When observed on the epithelial cell surface, Candida cells were either attached to host cells, or when infected tissue was stained with ruthenium red, Candida cells were observed on the epithelial surface embedded within an electron-dense matrix. Fungal elements were abundant in the submucosa at 24 h postinfection and were still observed on the epithelial cell surface; all of this was accompanied by an inflammatory response.

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