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At least 307 records · Page 17Linked to original sources
PubMed2000

Anti-CD9 monoclonal antibody-stimulated invasion of endometrial cancer cell lines in vitro: possible inhibitory effect of CD9 in endometrial cancer invasion.

Cell surface marker CD9 has been reported to play a role in inhibiting trophoblastic cell invasion. Since the invasive properties of cancer cells may resemble those of trophoblasts, we decided to investigate the role of CD9 in the invasion of endometrial cancer cells. In normal human endometrium, CD9 was found to be constitutively expressed on epithelial cells, as reported previously. While epithelial cells of endometrial hyperplasia (n = 5) were also positive for the expression of CD9, endometrial adenocarcinomas (n = 15) showed reduced expression. In order to clarify the significance of this reduced CD9 expression in endometrial cancer, an in-vitro invasion assay system was used to assess the effect of anti-CD9 monoclonal antibody (mAb) on the invasive properties of endometrial cancer cell line. Anti-CD9 mAb significantly enhanced invasion of the RL95-2 and Ishikawa cell lines, without affecting cell proliferation. Since CD9 is associated with the integrin subunits beta(1), alpha(3) and alpha(6) in human endometrium, we investigated the functional relationship between CD9 and these integrins in the RL95-2 cell line. Monoclonal antibodies against the integrins beta(1), alpha(3) and alpha(6) inhibited RL95-2 cell invasion. However, anti-CD9 mAb continued to show a stimulatory effect on RL95-2 cell invasion after treatment with anti-integrin alpha(3) mAb. In contrast, the anti-CD9 mAb had no effect after treatment with the mAb for integrins alpha(6) and beta(1). These findings indicate that CD9 is involved in regulating the invasive properties of endometrial carcinoma cells and that this effect is partially mediated by integrin subunits alpha(6) and beta(1). Thus, CD9 appears to be involved in the prevention of endometrial cancer invasion.

Adult↗
PubMed2002

Analysis of the roles of RGD-binding integrins, alpha(4)/alpha(9) integrins, alpha(6) integrins, and CD9 in the interaction of the fertilin beta (ADAM2) disintegrin domain with the mouse egg membrane.

Fertilin beta (also known as ADAM2), a mammalian sperm protein that mediates gamete cell adhesion during fertilization, is a member of the ADAM protein family whose members have disintegrin domains with homology to integrin ligands found in snake venoms. Fertilin beta utilizes an ECD sequence within its disintegrin domain to interact with the egg plasma membrane; the Asp is especially critical. Based on what is known about different integrin subfamilies and their ligands, we sought to characterize fertilin beta binding sites on mouse eggs, focusing on integrin subfamilies that recognize short peptide sequences that include an Asp residue: the alpha(5)/alpha(8)/alpha(v)/alpha(IIb) or RGD-binding subfamily (alpha(5)beta(1), alpha(8)beta(1), alpha(V)beta(1), alpha(V)beta(3), alpha(V)beta(5), alpha(V)beta(6), alpha(V)beta(8), and alpha(IIb)beta(3)) and the alpha(4)/alpha(9) subfamily (alpha(4)beta(1), alpha(9)beta(1), and alpha(4)beta(7)). We tested peptide sequences known to perturb interactions mediated by these integrins in two different assays for fertilin beta binding. Peptides with the sequence MLDG, which perturb alpha(4)/alpha(9) integrin-mediated interactions, significantly inhibit fertilin beta binding to eggs, which suggests a role for a member of this integrin subfamily as a fertilin beta receptor. RGD peptides, which perturb alpha(5)/alpha(8)/alpha(v)/alpha(IIb) integrin-mediated interactions, have partial inhibitory activity. The anti-alpha(6) antibody GoH3 has little or no inhibitory activity. An antibody to the integrin-associated tetraspanin protein CD9 inhibits the binding of a multivalent presentation of fertilin beta (immobilized on beads) but not soluble fertilin beta, which we speculate has implications for the role of CD9 in the strengthening of fertilin beta-mediated cell adhesion but not in initial ligand binding.

ADAM Proteins↗
PubMed2003

Identification and enrichment of spermatogonial stem cells displaying side-population phenotype in immature mouse testis.

In mammals, spermatogenesis is maintained by spermatogonial stem cells (SSC). In their niche, SSC divide to self-maintain and to produce a transit-amplifying population that eventually enters the meiotic cycle to give rise to spermatozoa. The low number of SSC and the lack of specific markers hinder their isolation and enrichment. Stem cells in several adult tissues can be identified by using their verapamil-sensitive Hoechst dye-effluxing properties, which define the characteristic "side population" (SP). Here we show, by multicolor flow cytometric analysis, that immature mouse testis contains a "side-population" (T-SP), which is Sca-1pos, Ep-CAMpos, EE2 pos, alpha6-integrin pos, and alpha(v)-integrin neg. A 13-fold enrichment in SSC activity was observed when sorted T-SP cells from ROSA 26 mice were transplanted in busulfan-treated mouse testis. Whereas an incomplete range of spermatogenic stages was encountered two months after transplantation of unsorted testicular cells, the transplantation of T-SP cells generated all associations of mouse germ cells representing the full range of spermatogenic stages. These data suggest that Hoechst staining and cell sorting might provide a novel approach to SSC enrichment in mammals.

Animals↗
PubMed2002

Histopathology of human corneas after amniotic membrane and limbal stem cell transplantation for severe chemical burn.

PURPOSE: To describe the histopathologic changes in the cornea following amniotic membrane transplantation (AMT) combined with limbal transplantation. METHODS: Four eyes with complete limbal stem cell deficiency after severe chemical burn underwent AMT with either a living-related conjunctival limbal allograft (lr-CLAL) (three eyes) or a conjunctival limbal autograft (CLAU) (one eye) for ocular surface reconstruction. Penetrating keratoplasty was performed several months after the initial procedure for further visual rehabilitation. Mean follow up time was 20 months. Light and transmission electron microscopy (TEM) and indirect immunofluorescence microscopy of the excised corneal buttons were performed. RESULTS: All specimens displayed a multilayered epithelium without conjunctival goblet cells over the entire corneal surface. Basal epithelial cells demonstrated a firm connection to the remnants of the transplanted amniotic membrane (AM), which at some places appeared to be in a state of "modification" or "remodeling" in the collagen layers. The basement membrane zone displayed a positive staining when using antibodies against collagen IV and VII, integrin alpha6 and beta4, laminin 5, and bullous pemphigoid antigen 2. Remnants of the AM in the specimen showed staining of collagen IV, which was found also in cross-sections of cryopreserved AM. The recipients Bowman's membranes that were only partially present after the initial trauma were significantly disturbed. CONCLUSION: Within the time frame studied, the transplanted AM apparently survives and integrates into the host tissue being modified or remodeled by recipient cells. AMT in combination with a CLAU or lr-CLAL is a useful technique in promoting a rapid and stable reepithelialization of a corneal surface following severe chemical or thermal damage.

Adolescent↗
PubMed2001

Alteration of integrins by interleukin-1alpha in human pancreatic cancer cells.

INTRODUCTION: Adhesion of tumor cells to extracellular matrix (ECM) proteins plays an important role in tumor invasion and metastasis. AIMS: To investigate the expression of integrins in human pancreatic cancer cell lines and its alteration by interleukin (IL)-1alpha to examine the mechanism of adhesion of metastatic human pancreatic cancer cells to ECM proteins. METHODOLOGY: The expression of integrin subunits and their alteration by IL-1alpha were examined by flow-cytometric analysis and cellular enzyme-linked immunosorbent assay in three metastatic human pancreatic cancer cell lines (AsPC-1, BxPC-3, and SW1990) and two nonmetastatic cancer cell lines (PaCa-2 and PANC-1). In addition, assays of cancer cell adhesion to ECM proteins were performed to investigate if increased integrin expression actually affected the adhesive interaction between cancer cells and the putative integrin ECM ligands. RESULTS: The alpha(6) subunit expressed in metastatic cancer cells was enhanced by IL-1alpha. Metastatic cancer cells also showed preferential adherence to laminin compared with nonmetastatic cancer cells, and this was enhanced by IL-1alpha. CONCLUSION: In pancreatic cancer, the enhancement of alpha(6)beta(1) integrin by IL-1alpha through IL-1 receptor type I, as well as the expression of alpha(6)beta(1) integrin, plays an important role in metastasis formation.

Antigens, CD↗
PubMed2004

Mechanisms of poly-N-acetyl glucosamine polymer-mediated hemostasis: platelet interactions.

BACKGROUND: Investigations were performed to determine whether poly-N-acetyl glucosamine (p-GlcNAc) induces hemostasis by the activation of platelets. METHODS: Platelets were isolated from human blood, fixed in the presence poly-N-acetyl glucosamine fibers, and visualized with scanning electron microscopy. Platelet activation surface markers were measured by fluorescence multiphoton microscopy. Platelet aggregation in the presence of p-GlcNAc fibers and integrin receptor blockers was measured. RESULTS: Scanning electron microscopy indicated that contact of platelets with poly-N-acetyl glucosamine fibers resulted in platelet activation. Fluorescent microscopy showed that contact of platelets with the marine polymer increased intracellular levels of free calcium and resulted in surface exposure of platelet phosphatidylserine, P selectin, and the alphaIIbbeta3 integrin. Antibody inhibitors of the platelet alphaIIbbeta3 integrin inhibited p-GlcNAc to stimulate fibrin polymerization. CONCLUSION: Poly-N-acetyl glucosamine fiber material promotes hemostasis by the activation of platelets.

Acetylglucosamine↗
PubMed2004

Integrin expression in cells of the intervertebral disc.

In this study, we investigated the profile of integrin expression in human and porcine intervertebral disc tissue. Differences in extracellular matrix composition between anulus fibrosus (AF) and nucleus pulposus (NP) regions of the disc, as well as differences in cellular responses to environmental stimuli, suggest a role for integrins in presenting matrix signals that may mediate these responses. Human disc tissue and porcine AF and NP tissue were stained with antibodies to alpha integrin subunits 1-6, V and IIb, and beta integrin subunits 1-6 and graded for evidence of positive staining on a scale from 0 (no staining) to 3 (high incidence of staining). Human tissue expressed alpha and beta integrin subunits shown to be present in articular cartilage, including alpha(1), alpha(5) and alpha(V). Porcine AF tissue expressed similar integrin subunits to human disc, with both expressing alpha(1), alpha(5), beta(1), beta(3) and beta(5) subunits, whereas porcine NP tissue expressed higher levels of alpha(6), beta(1) and beta(4) than AF tissue. The expressed subunits are known to interact with proteins including collagens, fibronectin and laminin; however, additional studies will be required to characterize the interactions of the integrin subunits with specific matrix constituents, as well as their specific involvement in regulating environmental stimuli.

Animals↗
PubMed2004

Ligation of the beta4 integrin triggers adhesion behavior of human keratinocytes by an "inside-out" mechanism.

Carcinogenesis is considered as a multistep process involving functional changes in the hemidesmosomal organization. In normal skin keratinocytes, expression of the alpha(6)beta(4) integrin is restricted to the proliferative basal layer and mediates stable adhesion to the underlying basement membrane. Observations in carcinoma cells show a functional and spatial dissociation of the alpha(6)beta(4) integrin from the hemidesmosomal complex, which stimulates cell migration and, therefore, may contribute to carcinoma invasion. We now have evaluated the adhesion behavior of epithelial cells at different stages of transformation in response to activation of the beta(4) integrin. It is demonstrated that ligation of the beta(4) integrin augmented adhesion of carcinoma and pre-carcinoma cells to non-modified plastic. In contrast, adhesion behavior of normal human keratinocytes was not influenced by ligation of the beta(4) integrin. In order to explain the mechanism of beta(4)-mediated adhesion, the hypothesis of an "inside-out" activation of integrins was tested. Evidence is given that for cells expressing the alpha(6)beta(4) integrin, ligation of the beta(4) integrin increased beta(1) integrin-mediated adhesion. Furthermore, ligation of the beta(4) integrin led to phosphorylation of PKB/Akt at both phosphorylation sites. Functional blocking of PKB/Akt by dominant-negative overexpression decreased cell adhesion in response to beta(4) integrin ligation. Taken together, the present data establish a link between the ligation of the beta(4) integrin and beta(1) integrin-mediated cell adhesion in carcinoma and pre-carcinoma cells. Hence, these findings provide further insight into the conversion processes during carcinogenesis and show the beta(4) integrin to be a key regulator of cellular adhesion.

Carcinoma, Squamous Cell↗
PubMed2005

Targeting Id1 and Id3 inhibits peritoneal metastasis of gastric cancer.

Inhibitor of DNA binding (Id) proteins are essential for cell differentiation, proliferation, migration, invasion and angiogenesis. Recently, they have been shown to correlate with less differentiated phenotypes, high malignant potential and poor clinical outcome in various kinds of tumors. In an attempt to develop new strategies for the treatment of peritoneal metastasis of gastric cancer, we prepared an Id1, 3 double-knockdown gastric cancer cell line, MKN45, by RNA interference and investigated its effects on the development of metastatic nodules in the peritoneal cavity. Both cell proliferation and migration capabilities were decreased in Id1, 3 double-knockdown cells, as was their ability to bind to laminin, which could be explained by the decreased expression of integrin alpha6. These are important steps in the metastatic process. In a mouse model, the number of peritoneal metastatic nodules formed by Id1, 3 double-knockdown cells was reduced compared to mock-transfected control cells, as was the size of individual tumors. In this study, we clearly demonstrated that Id1, 3 double-knockdown significantly impaired the ability of gastric cancer cells to form peritoneal metastasis. Id should be considered an ideal target for the treatment and prevention of gastric cancer, and RNA interference is an attractive and promising strategy to achieve it.

Animals↗
PubMed1998

Modulation of laminin integrin receptors in the postnatal and adult rat lung.

Recent studies have shown that type II pneumocytes, at birth and day 3 postnatally, have a diffuse distribution and localize at alveolar 'corners' between 3 and 7 days. Since alpha 3 beta 1 and alpha 6 beta 1 are laminin-binding receptors that are well expressed by rat type II alveolar epithelial cells, we postulated that they may play a role in the localization of the cells in the alveolus. To begin the evaluation of this hypothesis, we studied the temporal and spatial expression of the alpha 3, alpha 6, and beta 1 integrin subunit protein and mRNA in whole rat lungs during postnatal development by immunofluorescence, confocal microscopy, and Northern blot analysis. The temporal expression of proteins analyzed by immunochemistry, with integrin subunit specific antibodies, increased during the 3- to 7-day postnatal period and in adult lungs. Densitometric values of the alpha 3, alpha 6, and beta 1 mRNA expression, normalized to 28S rRNA, quadrupled from day 1 to day 3 postnatally. The mRNA expression of different integrin chains was elevated 1.5- to threefold from days 5 to 7 postnatally compared to day 1 levels. The alpha 3 and alpha 6 integrin subunit mRNA decreased to newborn levels in adult lungs, whereas the beta 1 integrin mRNA in adult lungs was expressed at approximately 50% of its level in newborn lungs. We postulate that the increases in alpha 3, alpha 6, and beta 1 integrin mRNA expression during the early neonatal period may be important for the spatial distribution of type II pneumocytes.

Aging↗
PubMed1996

Distribution of alpha 6 and beta 4 integrins following epithelial abrasion in the rabbit cornea.

Integrin complex alpha 6 beta 4 is a component of the hemidesmosome. In the unwounded cornea both the integrin subunits face the laminin-containing basement membrane, but the alpha 6 subunit is also located between the basal cells. While the migrating epithelium is known to be without hemidesmosomes, we investigated the distribution of alpha 6 beta 4 during epithelial healing. Epithelial abrasion 7.5 mm in diameter was mechanically created. The rabbits were killed 1-24 h or 2, 3, or 7 days later. Monoclonal antibodies against alpha 6, beta 4, and laminin A were used to detect their distributions by immunohistochemistry. Positive immunostaining for laminin A on the surface of the unepithelialized stroma indicated that basement membrane was intact after the epithelial abrasion. Three hours after corneal wounding, alpha 6, was detectable around the entire cell up to the leading edge of the migrating epithelium. In the peripheral wound, alpha 6, was also prominently present around the basal and suprabasal cells with only the superficial cell layers being negative. The beta 4 subunit showed a dissimilar distribution; it was not detectable subjacent to the leading edge. After 1 h the immunoreaction for the beta 4 subunit had faded 15 - 20 microns peripheral to the wound margin. Thereafter the subepithelial band was segmentally reassembled, starting from the periphery and progressing toward the central area of the wound. One week after epithelial wounding, immunolabeling for both integrin subunits was indistinguishable from that of the control cornea. Our results indicate that in addition to the beta 4 in the rabbit cornea, the alpha 6 subunit is also complex with another beta subunit during the epithelial healing phase. The results also suggest that basal cells 15 - 20 microns peripheral to the wound margin disassemble their HDs prior to the migration process.

Animals↗
PubMed1997

Expression of integrin subunits and CD44 isoforms in psoriatic skin and effects of topical calcitriol application.

Increasing evidence suggests involvement of integrins and CD44 isoforms in the pathogenesis of psoriasis, contributing to uncontrolled keratinocyte proliferation, neovascularization, and invasion of inflammatory cells. We have analyzed immunohistochemically in situ expression of integrins (CD29, CDw49b, CDw49c, CDw49e, CDw49f) and CD44 isoforms (CD44 standard, CD44 var/v6, CD44 v10) on frozen sections of normal and psoriatic skin (nonlesional skin, lesional skin before and along with topical calcitriol treatment). We did not observe visual changes of immunoreactivity in normal as compared to nonlesional psoriatic skin, while the staining pattern of CDw49c, CDw49f, and CD29 was severely altered in untreated lesional psoriatic skin. Most markedly, CDw49c, CDw49f, and CD29 were focally upregulated in suprapapillar epidermal compartments of lesional psoriatic skin, a staining pattern that is in accordance with the phenomenon that was described by Pinkus as "squirting papilla". Additionally, an increased proportion of inflammatory and endothelial cells revealed immunoreactivity for CD44(std.) in untreated lesional psoriatic as compared to nonlesional psoriatic or normal skin. After 8 weeks of topical calcitriol treatment (15 micrograms/g ointment), the staining pattern for CDw49c, CDw49f and CD29 was markedly changed in epidermis of lesional psoriatic skin, reverting to the staining pattern characteristic for the nonlesional psoriatic or normal human skin, although epidermal expression of CDw49f was still upregulated and CDw49e-, CDw49f-, CD29-, and CD44(std.)-immunoreactive inflammatory and endothelial cells were still to be found in the dermal compartment.

Administration, Topical↗
PubMed1994

Immunolocalization of alpha 2, alpha 5, and alpha 6 integrin subunits in salivary tissue and adenomas of the parotid gland.

The localization of the integrin subunits alpha 2, alpha 5, alpha 6 was studied immunohistochemically in samples of normal salivary gland and in a series of 8 pleomorphic adenomas, 5 Warthin's tumors, and 2 basal cell adenomas. In normal salivary tissue, acinar and ductal cells expressed alpha 2 and alpha 6 chains at the basal cell pole facing the basement membrane. alpha 2 also localized at sites of cell-cell contact. No staining of the epithelial component was seen with alpha 5. The polarized expression of alpha 2 and alpha 6 subunits was retained in salivary adenomas. These subunits were present at the basal cell pole of solid nests, tubules and ducts of pleomorphic adenomas, as well as of the basal layer of the epithelium of Warthin's tumor, and of the trabecular structures of basal cell adenomas. The alpha 5 subunit was consistently expressed only by cells embedded in the myxoid or chondroid matrix of pleomorphic adenomas. We conclude that the pattern of a integrin subunit expression in salivary adenomas may be related to the "epithelial" or "mesenchymal" phenotype of the neoplastic cells.

Adenolymphoma↗
PubMed1998

Immunodetection of cell adhesion molecules in rat Sertoli cell cultures.

PROBLEM: The presence of cell adhesion molecules (CAMs) in Sertoli cells has not been explored extensively. The expression of CAMs involved in cell-matrix and cell-to-cell interactions in Sertoli cell cultures was examined. METHOD OF STUDY: Immunohistochemical and Western blot techniques were applied to rat Sertoli cell cultures using specific antibodies to alpha 3, alpha 5, and alpha 6 integrin subunits; NCAM; and cadherins. RESULTS: Expression of alpha 3 and alpha 6 integrin subunits (mainly laminin receptors) and lack of expression of alpha 5 integrin subunit (fibronectin receptor) was observed in Sertoli cells by immunohistochemistry. These cells also expressed neural CAM (NCAM) and N-cadherin. By Western blot analysis, Sertoli cell extracts reacted with antibodies to alpha 3 integrin subunit revealed a band approximately 130 kDa, whereas no expression of alpha 5 integrin subunit was detected. Cell extracts incubated with antibodies to pan cadherin exhibited a band approximately 120 kDa, whereas bands of 180, 140, and 120 kDa were observed with antibodies to NCAM. CONCLUSION: New data about the expression of receptors for extracellular matrix proteins (alpha 3 and alpha 6 integrin subunits) as well as cell-to-cell adhesion molecules (NCAM and cadherins) are reported in rat Sertoli cell cultures.

Animals↗
PubMed1995

Changes in the expression of integrins and basement membrane proteins in benign mucous membrane pemphigoid.

OBJECTIVE: To determine the location of the subepithelial split in benign mucous membrane pemphigoid (BMMP) and its relationship to the anchoring filaments and their receptors. MATERIALS AND METHODS: Frozen sections of lesional and perilesional oral mucosa from 10 cases of BMMP were stained, using an immunofluorescence method, for the beta-1, beta-4, alpha-3 and alpha-6 integrin subunits and for their ligands, laminin I and laminin V (kalinin). In all cases the diagnosis was confirmed by the demonstration of linear staining for IgG at the basement membrane zone. Six specimens of normal mucosa were stained for comparison. RESULTS: Staining for integrins, laminin and kalinin in perilesional mucosa was similar to normals, although one case showed loss of alpha-6 and beta-4 . In lesional mucosa, laminin and kalinin showed strong linear staining localised to the floor of the bullae. The alpha-6 and beta-4 subunits were expressed only on the roof of the bullae but staining was weak and patchy with areas of loss. In some sections alpha-6 showed a punctate intracellular distribution similar to IgG. The distribution of alpha-3 and beta-1 was similar to that seen in normals. CONCLUSIONS: In all cases kalinin was found on the connective tissue side of the lesions and alpha-6 beta-4 localised to the epithelial side. This shows that the split occurs at a location which separates anchoring filaments from the hemidesmosomes. Loss of the alpha-6 beta-4 integrin in the lesions and the similar intracellular staining of alpha-6 and IgG, suggest that disruption of hemidesmosomes may be a key event in the immunopathogenesis of the lesions and that the alpha-6 integrin subunit is a potential antigen in oral mucosal BMMP.

Actin Cytoskeleton↗
PubMed2004

Anti-invasive gene expression profile of curcumin in lung adenocarcinoma based on a high throughput microarray analysis.

Curcumin has been reported to exhibit anti-invasive and/or antimetastatic activities, but the mechanism remains unclear. In this study, microarray analysis of gene expression profiles were used to characterize the anti-invasive mechanisms of curcumin in highly invasive lung adenocarcinoma cells (CL1-5). Results showed that curcumin significantly reduces the invasive capacity of CL1-5 cells in a concentration range far below its levels of cytotoxicity (20 microM) and that this anti-invasive effect was concentration dependent (10.17 +/- 0.76 x 10(3) cells at 0 microM; 5.67 +/- 1.53 x 10(3) cells at 1 microM; 2.67 +/- 0.58 x 10(3) cells at 5 microM; 1.15 +/- 1.03 x 10(3) cells at 10 microM; P < 0.05) in the Transwell cell culture chamber assay. Using microarray analysis, 81 genes were down-regulated and 71 genes were up-regulated after curcumin treatment. Below sublethal concentrations of curcumin (10 microM), several invasion-related genes were suppressed, including matrix metalloproteinase 14 (MMP14; 0.65-fold), neuronal cell adhesion molecule (0.54-fold), and integrins alpha6 (0.67-fold) and beta4 (0.63-fold). In addition, several heat-shock proteins (Hsp) [Hsp27 (2.78-fold), Hsp70 (3.75-fold), and Hsp40-like protein (3.21-fold)] were induced by curcumin. Real-time quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry confirmed these results in both RNA and protein levels. Curcumin (1 to 10 microM) reduced the MMP14 expression in both mRNA and protein levels and also inhibited the activity of MMP2, the down-stream gelatinase of MMP14, by gelatin zymographic analysis. Based on these data, it can be concluded that curcumin might be an effective antimetastatic agent with a mechanism of anti-invasion via the regulation of certain gene expressions.

Antineoplastic Agents↗
PubMed2003

Soluble extracts from Helicobacter pylori induce dome formation in polarized intestinal epithelial monolayers in a laminin-dependent manner.

Helicobacter pylori colonizes the stomach at the interface between the mucus layer and the apical pole of gastric epithelial cells. A number of secreted and shed products from the bacteria, such as proteins and lipopolysaccharide, are likely to have a role in the pathogenesis at the epithelial level. To determine the physiological response of transporting polarized epithelia to released soluble factors from the bacterium, we used the T84 cell line. Monolayers of T84 cells were exposed to soluble extracts from H. pylori. The extracts induced rapid "dome" formation as well as an immediate decrease in transepithelial electrical resistance. Domes are fluid-filled blister-like structures unique to polarized epithelia. Their formation has been linked to sodium-transporting events as well as to diminished adherence of the cells to the substrate. H. pylori-induced dome formation in T84 monolayers was exacerbated by amiloride and inhibited by ouabain. Furthermore, it was associated with changes in the expression of the laminin binding alpha 6 beta 4 integrin and the 67-kDa laminin receptor. Domes formed primarily on laminin-coated filters, rather than on fibronectin or collagen matrices, and their formation was inhibited by preincubating the bacterial extract with soluble laminin. This effect was specific to H. pylori and independent of the urease, vacA, cagA, and Lewis phenotype of the strains. These data indicate that released elements from H. pylori can alter the physiological balance and integrity of the epithelium in the absence of an underlying immune response.

Animals↗
PubMed2005

Human papillomavirus type 31b infection of human keratinocytes does not require heparan sulfate.

Oncogenic human papillomaviruses (HPVs) are difficult to study experimentally as they replicate at low levels in vivo. This has precluded the purification of high-risk HPV virions from in vivo lesions. Virus-like particles (VLPs) and pseudovirions from low- and high-risk HPV types can emulate various aspects of HPV virion attachment and infections. These studies suggest that HPV infection is mediated by alpha6-integrin and/or heparan-sulfonated receptors. However, whether VLPs and pseudovirions accurately reflect the infection process of HPV virions has not been verified. We generated infectious HPV31b virions from organotypic (raft) tissues and performed experimental infections in a variety of cells. Successful infection following viral attachment, internalization, and nuclear transport was assayed by detecting newly synthesized, spliced HPV transcripts using reverse transcription (RT)-PCR or RT-quantitative PCR. Most human epithelial cells were infected with HPV31b at a multiplicity of infection as low as 1 to 10 viral genome equivalents per cell. HPV31b infection was detected in other cell lines, including COS-7 monkey kidney cells, but higher viral multiplicities of infection were required. Heparin preparations of various molecular weights or heparinase I treatment of cells prevented HPV31b infection of COS-7 cells and C-33A human cervical cancer cells in reproducible and dose-dependent manners. However, these reagents were unable to block infection of human keratinocytes, including HaCaT and N/TERT-1 cells and low-passage human foreskin keratinocytes. These data suggest that HPV31b infection of human keratinocytes, the natural host cell for HPV infections in vivo, does not require a heparan-sulfonated receptor, whereas heparan sulfate is important for infection of some other cells.

Animals↗