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PubMed2002

Expression of extracellular matrix components in a highly infiltrative in vivo glioma model.

This work demonstrates the expression of extracellular matrix (ECM) components in a highly infiltrative brain tumor model developed by simple inoculation of spheroids from five human glioma biopsy tissues directly into the brains of immunodeficient rats. Non-invasive tumors derived from one glioblastoma biopsy specimen and two glioma cell lines (D-54MG and U-251MG) were also included in this study. The extent of tumor cell infiltration was studied using a pan-human monoclonal anti-vimentin antibody. The cellular origin for several of these ECM components was identified using human-specific monoclonal antibodies and polyclonal antibodies detecting epitopes from both species. Immunostaining revealed a diffuse parenchymal staining of glioma-produced tenascin, whereas vitronectin was produced mainly by the invading glioma cells. ECM components such as laminin, fibronectin and collagen type IV were most probably produced by the host and were mainly associated with the blood vessels in the tumors. However, some parenchymal staining with regional variations was observed. The expression pattern of these components was different in cell lines tumors as compared to the biopsy specimen tumors. The alpha3 and beta1 integrin subunits were mainly observed in areas of tumor cell invasion in the invasive tumors. In conclusion, the observed staining patterns clarify the cellular origin and indicate the possible biological function of tenascin, vitronectin, laminin, fibronectin and collagen type IV in these highly invasive malignant tumors of glial origin.

Animals↗
PubMed1997

Lymphocyte adhesion molecule ligands and extracellular matrix proteins in gliomas and normal brain: expression of VCAM-1 in gliomas.

To identify antigenic differences between gliomas and normal brain, we have immunohistochemically studied the expression of lymphocyte adhesion molecules (ICAM-1, ICAM-2, ICAM-3, VCAM-1, E-selectin and CD58), epidermal growth factor receptor (EGFR) and extracellular matrix proteins (collagen IV, fibronectin, laminin, merosin, tenascin and vitronectin) in these tissues. Gliomas expressed high levels of ICAM-1, CD58 (LFA-3), EGFR, tenascin and vitronectin, whereas only very low levels were detected in normal brain. VCAM-1 expression was detected in 15 out of 25 gliomas but not in normal brain. The presence of VCAM-1 in gliomas was verified by immunoblotting and RNase protection assay, and in glioma cell lines by Northern blotting. Expression of VCAM-1 in gliomas may partially explain lymphocytic infiltration, and anti-VCAM-1 antibodies may be of potential in antibody mixtures for targeted therapy of gliomas.

Adult↗
PubMed2006

Morphological analysis of integrin-mediated adhesion of immature human mast cells to extracellular matrix proteins.

Specific heterodimers of alpha and beta integrins are implicated in mediating adhesion and functional activation of mast cells to extracellular matrix (ECM) proteins, determining thus homing, secretion and tissue distribution of these cells. In the present study, we have examined integrin expression and associated morphological features of mast cells adhering to ECM, also depending on cell activation and under the influence of protein kinase C (PKC) inhibitors. Unstimulated and PMA-activated human leukaemic mast cells (HMC-1 line) were allowed to adhere to fibronectin or vitronectin-coated surfaces. Cells were specifically stained for actin, beta(1, )alpha(1)-alpha(6), alpha(v) and alpha(v)beta(5 )integrins and were evaluated by fluorescence microscopy and confocal laser scan microscopy. Spontaneously adhering cells rapidly assumed an oblong shape, with pronounced formation of filopodia, whereas PMA-stimulated cells were round in shape. Clustering of integrins on filopodia and on comma-like shapes at the cell circumference in rounded cells was noted only for alpha(4), alpha(5) and beta(1 )chains in fibronectin-adhering cells, and for alpha(v) and alpha(v)beta(5) chains in vitronectin-adhering cells. On double staining, clustered integrins co-localized with each other and with actin at the cell membrane and along intracellular tension lines of actin filaments. PKC inhibitors affected the shape of cells, but adhesion was maintained. These data provide a morphological correlate to previously reported functional studies, demonstrating clustering of selected integrins during ECM adhesion at the cell membrane. This was associated with alignment of integrins along actin filaments within the cytoplasm, PKC signalling and changes in shape and activation of mast cells.

Cell Adhesion↗
PubMed1997

Heterotypic cell-cell adhesion of human mast cells to fibroblasts.

Skin mast cells are typically located in the perivascular or perineural connective tissue. We observed that HMC-1 mast cells growing in suspension adhered efficiently to (> 90% of cells) and spread on top of fibroblast monolayers and to a lesser degree on purified extracellular matrix proteins. Since adhesive interactions determine cell migration and tissue localization we studied the mechanism. It was found that HMC-1 cells attach to collagen I and fibronectin, laminin, collagen IV and vitronectin, but not to collagens III and VI or hyaluronic acid. Adhesion to fibronectin, collagen I and laminin was completely inhibited by mAbs blocking beta 1-integrins, whereas adhesion of HMC-1 cells to vitronectin was inhibited by anti-alpha v-chain mAbs. However, attachment of HMC-1 cells to fibroblasts was not influenced by mAbs blocking beta 1- or alpha v-chain function, by RGD peptides or by mAbs interfering with other receptors, most notably c-kit. Identical results were obtained with normal mast cells isolated from human foreskin. These results indicate that human mast cells attach to fibroblasts independently of beta 1- or alpha v-integrins as well as of c-kit receptor-mediated mechanisms. The functional characteristics observed (i.e. only partial sensitivity to trypsin and EDTA, no increase in trypsin sensitivity by pretreatment with EDTA) suggest that cadherin receptors were not involved, and it is likely that the adhesion process observed involved not-yet-defined heterotypic cell-cell adhesion receptors.

Antibodies, Monoclonal↗
PubMed2005

Anti-migratory and anti-angiogenic effect of p16: a novel localization at membrane ruffles and lamellipodia in endothelial cells.

Recent evidence has established different functions for the tumor suppressor protein, p16(INK4A) aside from controlling the cell cycle. Here we report that cdk4/6 inhibition blocked both human umbilical vein endothelial cells (HUVEC) spreading on a vitronectin matrix and HUVEC migration on vitronectin. p16 can also act as an anti-angiogenic molecule in vitro since HUVEC and HMEC cells transfected with Ad-p16 or treated with Antennapedia p16 peptides are unable to differentiate on a Matrigel matrix. Both, p16, cyclin D1, cdk4 and cdk6 were immuno-colocalized with Ezrin, Rac, Vinculin, alphav-integrin, and FAK proteins in the ruffles and lamellipodia of migratory cells. Our results indicate that p16 is a key component of a new cytoplasmic pathway controlling angiogenesis of endothelial cells via the alphavbeta3-integrin-mediated migration.

Cell Membrane↗
PubMed1989

The GPIIB-IIIa-like complex may function as a human melanoma cell adhesion receptor for thrombospondin.

The purpose of this study was to determine whether a heterodimeric complex immunologically related to the fibrinogen receptor could function as a thrombospondin (TSP) receptor in TSP-mediated cell-substratum adhesion of human melanoma cells. We found that polyclonal antibodies to the platelet GPIIb-IIIa complex, GPIIIa, and the human vitronectin receptor inhibited TSP-mediated cell adhesion by 63-68%. Immunoprecipitation of detergent extracts of 125I-surface-labeled melanoma cells using either anti-human platelet GPIIb-IIIa or anti-human vitronectin receptor antibody revealed the presence of a single heterodimeric complex, suggesting that both antisera recognize the same integrin receptor, GPIIb-IIIa-like antigen. Adhesion of cells to TSP is likely mediated through a region of the TSP molecule containing the arginine-glycine-aspartic (RGD) peptide sequence, since cell attachment to TSP was inhibited 50-66% in the presence of peptides containing RGD. These results strongly suggest that a GPIIb-IIIa-like/vitronectin receptor can serve as a cell binding site for TSP in mediating cell-substratum adhesion.

Antibodies, Monoclonal↗
PubMed1990

RGD peptides may only temporarily inhibit cell adhesion to fibronectin.

When human fibroblasts were cultured on fibronectin for 4 h in the presence of 0.5 mg/ml of the GRGDSP peptide derived from the fibronectin cell-binding site, they adhered and spread normally and organized talin and integrin alpha 5 and beta 1 subunits into focal adhesions. When the adherent cells were quantitated as a function of time, submaximal peptide concentrations were found to delay cell adhesion on fibronectin, but they had no effect on the maximum. When the cells were plated on vitronectin, however, even relatively low peptide concentrations lowered the maximal amount of cells adhering and abolished cell spreading. The results suggest a different mechanism for cell adhesion on fibronectin and vitronectin.

Amino Acid Sequence↗
PubMed1991

The role of fibrinogen in mediating staphylococcal adherence to fibers.

The use of tampons and surgical gauze pads and colonization with Staphylococcus aureus have been established as risk factors for the development of toxic shock syndrome. To elucidate the role of blood factors in the mediation of staphylococcal adherence to fibers used in tampons and surgical packing, an adherence assay with cotton fibers was developed. Results demonstrated that cotton disks precoated with fibrinogen in the presence of human serum albumin bound a significant percentage of the inoculum for both staphylococcal strains tested when compared to human serum albumin controls. Likewise, fibers pretreated with plasma or defibrinated blood containing a small amount of fibrin revealed comparable staphylococcal adherence to that of fibrinogen. In contrast, fibers pretreated with serum, fibronectin, or vitronectin did not exhibit significant augmentation in staphylococcal attachment in comparison to human serum albumin controls. The attachment of staphylococci to fibrinogen and/or fibrin appeared to be specific and is blocked by goat anti-human fibrinogen antibody, but not fibronectin, vitronectin, or nonimmune goat IgG. Thus, our data indicate that fibrinogen/fibrin is the dominant blood component in the mediation of staphylococcal adherence to fibers used in tampons and surgical gauze pads.

Animals↗
PubMed1991

Molecular forms of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) in human plasma.

Molecular forms of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA), identified by gel filtration and specific immunoassays, were studied in plasma from subjects with normal and elevated PAI-1 levels before and after in vitro or in vivo addition of t-PA. In normal plasma, PAI-1 occurs in three molecular forms, a Mr greater than 700 KDa inactive form of heterogeneous composition, an active 450 KDa form containing PAI-1/vitronectin complex and an inactive peak at Mr 50 KDa containing free PAI-1. Stimulation of platelets results in a significant increase of the 50 KDA form and a slight increase of the 450 KDa form. Patients with increased PAI activity levels have an increase of both the 450 KDa and the 50 KDa forms, whereas patients with thrombotic thrombocytopenic purpura have an increased 50 KDa form. In normal plasma, collected in the presence or absence of D-Phe-Pro-Arg-CH2Cl, t-PA occurs primarily as a Mr greater than 700 KDa form containing t-PA/PAI-1 complex. Addition of high concentrations of t-PA (70 ng/ml) to plasma in vitro or t-PA injection in vivo, results in t-PA inhibitor complexes, including t-PA/ alpha 2 antiplasmin. It is concluded that in subjects with increased PAI-1 levels in plasma, PAI-1 may occur as high molecular weight complexes with vitronectin of which 450 KDa was the most important part and as a 50 KDa inactive form; t-PA circulates primarily in complex with inhibitors. Thus, some of the molecular interactions between PAI-1, t-PA and vitronectin, previously demonstrated in purified systems in vitro, also occur in plasma.

Amino Acid Sequence↗
PubMed1989

Purification of high and low molecular weight plasminogen activator inhibitor 1 from fibrosarcoma cell-line HT 1080 conditioned medium.

Functionally active (high-Mr) and inactive (low-Mr) plasminogen activator inhibitor 1 (PAI) have been purified from fibrosarcoma cell-line HT 1080 conditioned medium, containing 1% fetal calf serum. The two forms were first purified by affinity chromatography on heparin-Sepharose and then separated from each other by gel filtration on Sephadex G-150. The final purification was achieved by affinity chromatography on insolubilized monoclonal antibodies towards human PAI. Alternatively, the low-Mr form was purified by chromatography on carboxymethyl-cellulose. Low-Mr PAI purified in this way, could be almost fully reactivated by treatment with guanidinium chloride. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis followed by immunoblotting revealed that the low-Mr form contained nothing but PAI at an Mr of about 50,000. In addition to PAI, the high-Mr form contained a component, which was not antigenically related to PAI. This compound had a molecular weight of about 75,000 and its NH2-terminal amino acid sequence corresponded to that of human vitronectin. We conclude that the high-Mr form of PAI constitutes a complex between 50,000 Mr PAI and vitronectin from fetal calf serum.

Amino Acid Sequence↗
PubMed1995

Cathepsin D-like aspartyl protease activity mediates the degradation of tissue-type plasminogen activator/plasminogen activator inhibitor-1 complexes in human monocytes.

Plasminogen activator inhibitor-1 (PAI-1) is the most important inhibitor of tissue-type plasminogen activator (t-PA) in plasma and plays a major role in the regulation of fibrinolysis. Plasma t-PA/PAI-1 complexes are cleared via a receptor-dependent mechanism in hepatocytes, while the fate of complexes formed in the extracellular matrix and in thrombi is less well understood. In this study, the degradation of t-PA/PAI-1 complexes by monocytes was examined. THP-1 monocytoid cells and freshly isolated human monocytes internalize and degrade [125I]t-PA/PAI-1 complexes at rates of 11.4 +/- 5.9 (mean +/- S.D.) and 44.6 +/- 6.3 ng/10(6) cells/h, respectively. Degradation is blocked by receptor-associated protein (RAP), indicating a member of the low density lipoprotein (LDL) receptor family is involved in the uptake/degradation of t-PA/PAI-1 complexes by monocytes. Degradation of t-PA/PAI-1 complexes is also inhibited by chloroquine and by pepstatin A, suggesting that a lysosomal aspartyl protease is likely involved. SDS-PAGE and Western blotting demonstrated that the purified lysosomal aspartyl protease, cathepsin D, is capable of digesting t-PA (t1/2 15 min), active PAI-1 (t1/2 2 h), and t-PA/PAI-1 complex (t1/2 30 min). Cathepsin D sequentially cleaves PAI-1 after hydrophobic amino acids, yielding lower molecular weight fragments. PAI-1 conformation influences the degradative efficiency of cathepsin D, with vitronectin-bound PAI-1 and latent PAI-1 exhibiting resistance to proteolysis and > 10-fold prolongation in t1/2. These data provide evidence that t-PA/PAI-1 complexes are internalized by human monocytes via a member of the low density lipoprotein (LDL) receptor family, and identifies cathepsin D-like aspartyl protease activity as largely responsible for the degradation of these complexes. Furthermore, vitronectin-bound PAI-1 and latent PAI-1 are relatively resistant to degradation by cathepsin D, which may be of importance in complex physiological environments.

Cathepsin D↗
PubMed1994

Triflavin, an Arg-Gly-Asp-containing peptide, inhibits human cervical carcinoma (HeLa) cell-substratum adhesion through an RGD-dependent mechanism.

Triflavin, a 7.5-kDa cysteine-rich polypeptide purified from Trimeresurus flavoviridis snake venom, belongs to a family of RGD-containing peptides, termed disintegrins, that have been isolated from the venoms of various vipers and shown to be potent inhibitors of platelet aggregation. The interaction of tumor cells with extracellular matrices such as fibronectin, vitronectin, and collagen has been shown to be mediated through a family of cell surface receptors that specifically recognize an arginine-glycine-aspartic acid (RGD) sequence within each adhesive protein. In this study, we show that triflavin dose-dependently inhibited adhesion of human cervical carcinoma (HeLa) cells to extracellular matrices (ECMs; i.e., fibronectin, fibrinogen, and vitronectin). On the other hand, triflavin exerted a limited inhibitory effect on cell adhesion to laminin and collagen (type I and IV). On a molar basis, triflavin is approximately 800 times more potent than Gly-Arg-Gly-Asp-Ser (GRGDS) at inhibiting cell adhesion. When immobilized on plate, triflavin significantly promoted HeLa cell adhesion, and this attachment was inhibited by GRGDS. Furthermore, FITC-conjugated triflavin bound to cells in a saturable manner and its binding was inhibited by GRGDS. In addition, triflavin did not affect [3H]thymidine uptake of HeLa cells during a 3-day incubation. These results suggest that triflavin probably binds to integrin receptors expressed on HeLa cell surface via its RGD sequence within its molecule, thereby inhibiting the adhesion of extracellular matrices to HeLa cells.

Amino Acid Sequence↗
PubMed1996

Influence of extracellular matrix proteins on human keratinocyte attachment, proliferation and transfer to a dermal wound model.

The aim of this study was to investigate whether prior culture of cells on ECM proteins might positively influence the performance of keratinocytes when cells are transferred to a dermal in vitro wound bed model. Keratinocytes were cultured using a method for producing cultured epithelial autografts for severely burned patients (essentially using Green's medium, a mitogen-rich medium containing fetal calf serum, cholera toxin, EGF, insulin, transferrin and triiodothyronine). Cells were cultured either on irradiated 3T3 fibroblasts (as in the standard Rheinwald and Green technique) or, alternatively, on collagen I, collagen IV, matrigel, RGD, vitronectin or fibronectin. Under these conditions matrigel, collagen I and IV enhanced initial attachment, RGD, vitronectin, fibronectin and irradiated 3T3 fibroblasts did not. Proliferation of cells was positively influenced by matrigel, collagen I and IV and irradiated 3T3 fibroblasts; of these, however, only matrigel and 3T3 fibroblasts had sustained significant effects on keratinocyte proliferation over 4 days. Cells on fibronectin showed significantly reduced proliferation. An acellular non-viable dermis was then used to mimic the homograft allodermis onto which cultured epithelial autograft sheets are grafted clinically and cells cultured on the various ECM proteins for 96 h were transferred to this in vitro wound model. None of the substrates enhanced keratinocyte performance on this model. It was concluded that under these conditions some ECM proteins can significantly affect keratinocyte attachment and, to a lesser extent, proliferation but that the culture of keratinocytes on these ECM proteins does not appear to confer any lasting benefit to the attachment of these keratinocytes to an in vitro wound-bed model.

Cell Division↗
PubMed2005

Cell adhesive PET membranes by surface grafting of RGD peptidomimetics.

A non-peptide mimic of the Arg-Gly Asp (RGD) active sequence of adhesive proteins (such as vitronectin) has been equipped with two different spacer-arms for surface anchorage. The covalent grafting on poly(ethylene terephthalate) (PET) membrane was realized via the activation of the hydroxyl polymer chain-ends by tosylation followed by nucleophilic substitution. The surface density of peptidomimetics was determined by X-ray photoelectron spectroscopy (XPS), on the basis of F/C atomic ratios since a fluorine tag was incorporated into the RGD-like compounds. The biological activity of soluble peptidomimetics was evaluated versus isolated human integrin alpha(v)beta(3) (vitronectin receptor), and versus CaCo2 cells. Inhibition of cellular adhesion was observed after pre-incubation of CaCo2 cells with soluble peptidomimetics. On the other hand a significant promotion of cellular adhesion resulted from the surface grafting of peptidomimetics on the PET culture substrate. The best performance was obtained with the RGD-like integrin ligand bearing a triethylene glycol spacer-arm.

Cell Adhesion↗
PubMed2005

Controlling the phenotype and function of mesenchymal stem cells in vitro by adhesion to silane-modified clean glass surfaces.

The behaviour of human mesenchymal stem cells (hMSC) when cultured in contact with a range of silane-modified surfaces was examined to determine if changing the surface chemistry affected the early differentiation potential of mesenchymal stem cells in vitro over a 7-day period. Cells were cultured for 1 and 7 days in direct contact with glass which had been functionalized by surface treatment to provide a range of different surfaces: -CH(3), -NH(2), -SH, -OH, and -COOH modified surfaces and a clean glass reference (TAAB). Viable cell adhesion was quantified by Lactate Dehydrogenase assay, and morphology and viability was qualitatively evaluated using calcein AM, ethidium homodimer, cytoskeletal (F Actin), extra-cellular matrix (fibronectin and vitronectin) and Hoechst staining (nucleus). The expression of selected differentiation markers, Collagen II (chondrocytes), CBFA1 (bone transcription factor), Collagen I (MSC marker) and TGF-beta3 (extra-cellular matrix production) was determined using real time polymerase chain reaction. The expression of ornithine decarboxylase was evaluated as a marker of proliferation. Surfaces of the -NH(2) group demonstrated the greatest level of cell adhesion by the 7-day period, and mRNA expression profiles indicated osteogenic differentiation, increased CBFA1 and decreased Collagen II expression. Cells cultured in contact with the -COOH surfaces displayed different cell morphologies, fibronectin and vitronectin spatial distributions compared with the cells in contact with the -NH(2) surfaces, in addition to an increase in Collagen II expression, indicative of chondrogenic differentiation. The modifications to the surface chemistry of glass did affect cell behaviour, both in terms of viable cell adhesion, morphology and profiles of mRNA expression, providing the means to alter the differentiation potential of the MSCs.

Cell Adhesion↗
PubMed2004

The involvement of integrin alphavbeta3 in polymorphonuclear leukocyte-induced angiogenesis in bovine aortic endothelial cells.

We have previously reported that angiogenesis stimulated by adhesion of polymorphonuclear leukocytes (PMNs) to endothelial cells (ECs) via intercellular adhesion molecule-1 (ICAM-1) might be mediated by a transcription factor, ets-1, which regulates adhesion molecules such as integrins related to angiogenesis. However, the regulation mechanisms of PMN-induced angiogenesis mediated by ICAM-1 remain unclear. Therefore, we investigated the effects of PMN on EC attachment to the extracellular matrix (ECM), which is one of the critical elements for angiogenesis development. After the addition of PMNs, attachment of bovine aortic endothelial cells (BAECs) to vitronectin, which is known as a ligand for integrin alpha(v)beta(3), increased greatly. Stimulation of BAEC with PMN induced expressions of integrin beta(3) mRNA and protein. PMN-induced angiogenesis was inhibited by Arg-Gly-Asp (RGD) peptide and LM609 anti-alpha(v)beta(3) antibody. The PMN-induced BAEC attachment to vitronectin was inhibited by ets-1 antisense oligonucleotide and anti-ICAM-1 antibody. These results suggested that enhancement of EC attachment to ECM via integrin alpha(v)beta(3) participated in the development of PMN-induced angiogenesis. Furthermore, the increase in EC attachment to ECM by ligation of PMN to ICAM-1 might be regulated by Ets-1 expression.

Animals↗
PubMed2006

Laminin-5 activates extracellular matrix production and osteogenic gene focusing in human mesenchymal stem cells.

We recently reported that laminin-5, expressed by human mesenchymal stem cells (hMSC), stimulates osteogenic gene expression in these cells in the absence of any other osteogenic stimulus. Here we employ two-dimensional liquid chromatography and tandem mass spectrometry, along with the Database for Annotation, Visualization and Integrated Discovery (DAVID), to obtain a more comprehensive profile of the protein (and hence gene) expression changes occurring during laminin-5-induced osteogenesis of hMSC. Specifically, we compare the protein expression profiles of undifferentiated hMSC, hMSC cultured on laminin-5 (Ln-5 hMSC), and fully differentiated human osteoblasts (hOST) with profiles from hMSC treated with well-established osteogenic stimuli (collagen I, vitronectin, or dexamethazone). We find a marked reduction in the number of proteins (e.g., those involved with calcium signaling and cellular metabolism) expressed in Ln-5 hMSC compared to hMSC, consistent with our previous finding that hOST express far fewer proteins than do their hMSC progenitors, a pattern we call "osteogenic gene focusing." This focused set, which resembles an intermediate stage between hMSC and mature hOST, mirrors the expression profiles of hMSC exposed to established osteogenic stimuli and includes osteogenic extracellular matrix proteins (collagen, vitronectin) and their integrin receptors, calcium signaling proteins, and enzymes involved in lipid metabolism. These results provide direct evidence that laminin-5 alone stimulates global changes in gene/protein expression in hMSC that lead to commitment of these cells to the osteogenic phenotype, and that this commitment correlates with extracellular matrix production.

Blotting, Western↗
PubMed2005

Inhibitory effects of Porphyromonas gingivalis fimbriae on interactions between extracellular matrix proteins and cellular integrins.

Porphyromonas gingivalis is a predominant periodontal pathogen, whose fimbriae are considered to be a major virulence factor, especially for bacterial adherence and invasion of host cells. In the present study, we investigated the influence of fimbriae on the interactions between alphavbeta3- and alpha5beta1-integrins and their ligand extracellular matrix (ECM) proteins (vitronectin and fibronectin), using human alphavbeta3- and alpha5beta1-integrin-overexpressing CHO cell lines (CHOalphavbeta3 and CHOalpha5beta1, respectively). P. gingivalis was found to have significantly greater binding to CHOalphavbeta3 and CHOalpha5beta1 than to control cells, whereas a fimbria-deficient mutant showed negligible binding to any of the tested cell lines. CHOalphavbeta3 and CHOalpha5beta1 cells attached to the polystyrene culture dishes in the presence of their ligand ECM proteins, while fimbriae markedly inhibited those attachments in a dose-dependent manner, with the highest dose of fimbriae achieving complete inhibition. In addition, the binding of vitronectin and fibronectin to CHOalphavbeta3 and CHOalpha5beta1 was inhibited by P. gingivalis cells. These results suggest that P. gingivalis fimbriae compete with ECM proteins for alphavbeta3- and alpha5beta1-integrins, and inhibit integrin/ECM protein-related cellular functions.

Animals↗