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PubMed1997

Ligation of integrin alpha5beta1 is required for internalization of vitronectin by integrin alphavbeta3.

Remodeling of the matrix by tumor cells is necessary for tumor invasion. We have shown previously that malignant astrocytomas, in contrast to normal astrocytes, synthesize vitronectin and express integrins alphavbeta3 and alphavbeta5. The activity states of these two integrins are differentially controlled. Thus, we investigated the regulation of the activity of integrins alphavbeta3 and alphavbeta5 with regard to their role in vitronectin internalization in U-251MG astrocytoma cell monolayers adherent to fibronectin, collagen, or laminin in serum-free conditions. Binding of [125I]vitronectin occurred in a specific, saturable manner that was partially inhibitable by monoclonal antibodies (mAbs) specific for integrins alphavbeta3 or alphavbeta5. Specific, lysosomally-mediated degradation of [125I]vitronectin was detectable at 1 h and increased over the 24-h assay period. The cell substrate affected the rate of turnover of [125I]vitronectin, which was 3.0 ng/min for cells plated on fibronectin but 0.35 ng/min for cells plated on collagen. Furthermore, although mAbs specific for either integrin alphavbeta3 or alphavbeta5 inhibited degradation (30%; combined effect 70%) of [125I]vitronectin by cells plated on fibronectin, only mAb anti-alphavbeta5 inhibited degradation (70-90%) by cells plated on collagen or laminin. To determine the requirement for integrin alpha5beta1 ligation in order for integrin alphavbeta3 to internalize its ligand, cells were plated on mAbs anti-integrin alpha5 or anti-integrin alpha3. When plated on mAb anti-alpha5, mAbs anti-alphavbeta3 and anti-alphavbeta5 both inhibited degradation. However, when plated on mAb anti-alpha3, mAb anti-alphavbeta3 had no effect whereas mAb anti-alphavbeta5 inhibited degradation. These data indicate that a signal from integrin alpha5beta1 is necessary for integrin alphavbeta3 to internalize vitronectin, whereas integrin alphavbeta5 constitutively internalizes vitronectin.

Astrocytoma↗

PubMed1992

Motility of fibronectin receptor-deficient cells on fibronectin and vitronectin: collaborative interactions among integrins.

Cells are capable of adhering to and migrating on protein components of the extracellular matrix. These cell-matrix interactions are thought to be mediated largely through a family of cell surface receptors termed integrins. However, the manner in which individual integrins are involved in cell adhesion and motility has not been fully determined. To explore this issue, we previously selected a series of CHO variants that are deficient in expression of the integrin alpha 5 beta 1, the "classical" fibronectin receptor. Two sets of subclones of these variants were defined which respectively express approximately 20% or 2% of fibronectin receptor on the cell surface when compared to wild-type cells (Schreiner, C. L., J. S. Bauer, Y. N. Danilov, S. Hussein, M. M. Sczekan, and R. L. Juliano. 1989. J. Cell Biol. 109:3157-3167). In the current study, the variant clones were tested for haptotactic motility on substrata coated with fibronectin or vitronectin. Data from assays using fibronectin show that cellular motility of the 20% variants was substantially decreased (30-75% of wild type), while the motility of the 2% variants was nearly abolished (2-20% of wild type). Surprisingly, a similar pattern was seen for haptotactic motility of both 2% and 20% variants when vitronectin was used (approximately 20-30% of wild type). The reduced haptotactic motility of the fibronectin receptor-deficient variant clones on vitronectin was shown not to be due to reduced vitronectin receptor (alpha v beta 3) expression nor to a failure of these variants to adhere to vitronectin substrata. Transfection of the deficient variants with a cDNA for the human alpha 5 subunit resulted in normal levels of fibronectin receptor expression (as a human alpha 5/hamster beta 1 chimera) and restored the motility of the CHO variants on fibronectin and vitronectin. This indicates that expression of the alpha 5 subunit is required for normal haptotactic motility on vitronectin substrata and suggests that the fibronectin receptor (alpha 5 beta 1) plays a cooperative role with vitronectin receptors in cell motility.

Animals↗

PubMed1992

Extracellular matrix stimulation of guinea pig megakaryocyte proplatelet formation in vitro is mediated through the vitronectin receptor.

We have used an in vitro culture system to study the role of extracellular matrix (ECM) in the fragmentation of guinea pig bone marrow megakaryocytes (MK) and the formation of proplatelet fragments from these cells. Proplatelet formation is stimulated by culturing the cells on a hydrated type I collagen gel in the presence of serum. MK express integrin proteins alpha 5, alpha 6, beta 1, and the alpha v beta 3 complex as demonstrated by immunofluorescence. A monoclonal antibody, LM 609, to the alpha v beta 3 vitronectin receptor blocked proplatelet formation, whereas the monoclonal antibodies to the beta 1, alpha 5, and alpha 6 integrin proteins did not inhibit proplatelet formation. The tetrapeptide Arg-Gly-Asp-Ser (RGDS) inhibits proplatelet formation; however, there was no inhibition by the fibronectin receptor-specific peptide GRGDdSP. The fibrinogen gamma chain peptide HHLGGAKQAGDV, which binds to the platelet membrane glycoprotein complex IIb-IIIa but not to the vitronectin receptor (VnR), did not inhibit proplatelet formation, nor did two different laminin peptides. In the absence of serum, 5.7% of MK spontaneously formed processes or fragmented. The addition of 50 micrograms/ml of vitronectin to serum-free cultures increased proplatelet formation to 21.5% of the MK, equal to cultures with 10% serum. Stimulation of proplatelet formation by vitronectin in serum-free cultures was inhibited by LM 609. Antibody staining with anti-bovine vitronectin antibody showed that MK contain intracellular vitronectin. These data show that guinea pig MK express alpha 5, alpha 6, beta 1, and alpha v beta 3 integrins. However, only the MK vitronectin receptor and its interaction with vitronectin plays an essential role in proplatelet formation in vitro.

Amino Acid Sequence↗

PubMed1991

Platelet fibrinogen and vitronectin in Glanzmann thrombasthenia: evidence consistent with specific roles for glycoprotein IIb/IIIA and alpha v beta 3 integrins in platelet protein trafficking.

To assess the individual contributions of the platelet glycoprotein (GP) IIb/IIIa receptor and the alpha v beta 3 vitronectin receptor to platelet levels of fibrinogen and vitronectin, we analyzed the platelets from two groups of Glanzmann thrombasthenic patients: Iraqi-Jews, whose platelets lack both receptors, and Arab patients in Israel, whose platelets lack GPIIb/IIIa, but have normal or increased numbers of alpha v beta 3 vitronectin receptors. The platelets from both thrombasthenic groups had profound deficiencies of fibrinogen, but the defect in the Iraqi-Jewish patients' platelets appeared to be slightly more severe. This finding indicates that GPIIb/IIIa is the major determinant of platelet fibrinogen, presumably acting by receptor-mediated uptake, and that the alpha v beta 3 vitronectin receptor plays little or no role. Arab patients' platelets have normal amounts of platelet vitronectin, whereas Iraqi-Jewish patients' platelets have nearly five times as much vitronectin as control or Arab patients' platelets. To account for these data, we propose a working hypothesis in which vitronectin is synthesized in megakaryocytes and the alpha v beta 3 vitronectin receptor is involved in transport of the protein out of megakaryocytes and/or platelets. Collectively, these observations suggest that in addition to their recognized roles in cell adhesion and in the interaction of cells with extracellular proteins, integrin receptors may be important in protein trafficking into, and perhaps out of, platelets.

Blood Platelets↗

PubMed1999

Altered vitronectin receptor (alphav integrin) function in fibroblasts adhering on hydrophobic glass.

Function of integrins is crucial for adhesion, movement, proliferation, and survival of cells. In a recent study we found impaired fibronectin receptor function on hydrophobic substrata (G. Altankov et al. J Biomater Sci Polym Edn 1997;8:712-740). Here, we have studied the distribution and function of the vitronectin receptor (alphav integrin) in fibroblasts adhering on hydrophilic glass and hydrophobic octadecyl glass (ODS). The morphology of fibroblasts and the organization of actin cytoskeleton were studied and found to be altered on ODS, where the cells did not spread and possessed condensed actin. Pretreatment of the surfaces with serum or pure vitronectin improved cell morphology on both substrata, resulting in the development of longitudinal actin stress fibers. It was found with biotinylated vitronectin that comparable quantities of vitronectin were adsorbed from single vitronectin solutions or serum on glass and on hydrophobic ODS. The organization of the vitronectin receptors on the ventral cell surface was investigated in permeabilized cells showing normal focal adhesions in fibroblasts plated on glass but none of these structures on ODS. The distribution of alphav integrin on the dorsal cell surface was studied on nonpermeabilized living cells after antibody tagging. While fibroblasts adhering on plain or serum-treated glass developed a linear organization of alphav integrin, cells on plain and serum-treated ODS were not able to reorganize the vitronectin receptor. Studies on signal transduction with antiphosphotyrosine antibodies revealed co-localization of alphav integrin and phosphotyrosine in focal adhesions on glass and serum-treated glass. However, signaling was almost absent on plain ODS and weak on serum-treated ODS. It was concluded that alterations in vitronectin receptor function on the ventral cell surface caused by the hydrophobic material surface inhibit signal transfer and subsequent intracellular events that are important for the organization and function of integrins.

Actins↗

PubMed1994

Vitronectin in colorectal adenocarcinoma--synthesis by stromal cells in culture.

We have investigated the expression and cellular source of vitronectin in colorectal adenocarcinoma. Immunofluorescence staining of tissue sections revealed the presence of vitronectin in the stroma of the 11 tumors studied, but not in adjacent normal colon. A method was devised for the isolation from colorectal adenocarcinomas of fibroblast-like cells that stained positive for vimentin but negative for cytokeratin. These tumor-derived stromal cells synthesized and secreted vitronectin, as revealed by metabolic labeling and immunoprecipitation. This was confirmed by Southern blot analysis of polymerase chain reaction amplification products from reverse-transcribed RNA. Normal skin fibroblasts did not synthesize vitronectin. Immunofluorescence staining showed vitronectin deposited at focal contact sites in the tumor-derived cells, where it colocalized with vinculin and the alpha v integrin subunit. The deposition of vitronectin into focal contact sites was not dependent on the presence of serum. The finding that vitronectin can be synthesized and secreted by tumor-derived fibroblast-like cells in culture indicates that vitronectin expression can be promoted by as yet unknown signals provided in disease states, such as cancer.

Adenocarcinoma↗

PubMed1997

Plasminogen activator inhibitor-1 represses integrin- and vitronectin-mediated cell migration independently of its function as an inhibitor of plasminogen activation.

Cell migration involves the integrins, their extracellular matrix ligands, and pericellular proteolytic enzyme systems. We have studied the role of plasminogen activator inhibitor-1 (PAI-1) in cell migration, using human amnion WISH cells and human epidermoid carcinoma HEp-2 cells in an assay measuring migration from microcarrier beads and a modified Boyden-chamber assay. Active, but not latent or reactive center-cleaved, PAI-1 inhibited migration. A PAI-1 mutant without ability to inhibit plasminogen activation was as active as wild-type PAI-1 as a migration inhibitor, showing that inhibition of plasminogen activation was not involved. PAI-1 specifically interfered with intergrin- and vitronectin-mediated migration: Migration onto vitronectin-coated but not onto fibronectin-coated surfaces was inhibited by PAI-1, a cyclic RGD peptide inhibited migration, and both cell lines expressed vitronectin-binding alpha v-integrins. In addition, active PAI-1, but not latent or reactive center-cleaved PAI-1, inhibited vitronectin binding to integrins in an in vitro binding assay, without affecting binding of fibronectin. Monoclonal antibodies against the urokinase receptor, another vitronectin binding protein, did not affect cell migration in the beads assay, while some inhibitory effect was observed in the Boyden-chamber assay. We conclude that PAI-1, independently of its role as a proteinase inhibitor, inhibits cell migration by competing for vitronectin binding to integrins, while the interference of PAI-1 with binding of vitronectin to the urokinase receptor may play a secondary role. These data define a novel function for the serpin PAI-1, enabling it to regulate cell migration over vitronectin-rich extracellular matrix in the body.

Amnion↗

PubMed1994

The significance of vitronectin in proliferative diabetic retinopathy.

Vitronectin, an integrin-binding a-1-glycoprotein with potent cell-adhesion and proliferation-mediating properties, has been shown to be incorporated in surgically removed membranes from patients with proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR) and macular pucker. Therefore we developed an ELISA technique to quantify levels of vitronectin in human vitreous and plasma samples in order to be able to evaluate the significance of vitronectin in these different vitreoretinal diseases. Our results indicate a significant increase of vitronectin in all proliferative disorders except idiopathic macular pucker. Adjustment of all probes to equal total protein content yielded a significant increase only in PDR (type II diabetes). Plasma samples demonstrated a significant increase of vitronectin in patients with type II diabetes suffering from PDR. Therefore, break-down of the blood-retina barrier appears to be the most likely explanation for the increased levels of vitronectin in the vitreous. Our results indicate that vitronectin may not only be involved in the regulation of epiretinal membrane formation at significantly higher levels in patients with type II diabetes, but the increase of vitronectin in diabetic plasma may also help to explain the pathological alteration of the coagulation cascade in diabetics.

Blotting, Western↗

PubMed1987

Immunohistochemical demonstration of vitronectin in association with elastin and amyloid deposits in human kidney.

The multifunctional glycoprotein vitronectin, also called serum spreading factor and S-protein of complement, is a potent inducer of cell adhesion and spreading in vitro, and also has a regulatory function in the complement and coagulation pathways. It is present both in plasma and tissue. Recently, vitronectin immunoreactivity was demonstrated in the elastic fibres of normal human skin. Normal and amyloid kidney tissue was investigated for vitronectin immunoreactivity using polyclonal and monoclonal antibodies in an avidin-biotin-peroxidase complex technique and in an alkaline phosphatase anti-alkaline phosphatase complex technique. Vitronectin was found in the elastic layers of normal vessel walls, and in glomerular sclerotic lesions in cases of benign nephrosclerosis, but not in normal glomeruli. Strong specific vitronectin immunoreactivity was found in the amyloid deposits in kidneys from cases with amyloid A type amyloidosis, and in cases with amyloid light chain type amyloidosis. Structures immunostainable with anti-amyloid A antiserum were invariably immunostainable with anti-vitronectin. An antiserum against serum amyloid P component stained the same structures as did the anti-vitronectin antibodies, and in addition stained normal glomerular basement membranes. In conclusion, vitronectin immunoreactivity was demonstrated in elastic tissue, in amyloid deposits and in sclerotic lesions in human kidney.

Amyloid↗

PubMed1996

Collagen-binding activity of plasma vitronectin in chronic liver disease.

The collagen-binding activity of plasma vitronectin was measured in 15 control subjects and 64 subjects with chronic liver disease. The assay of collagen-binding vitronectin was performed by an enzyme immunoassay using a monoclonal antibody to human vitronectin and type I collagen from human placenta. The plasma collagen-binding vitronectin concentration (mean +/- S.D.) was 5.6 +/- 1.9 micrograms/ml in the controls, 8.3 +/- 1.1 micrograms/ml in chronic persistent hepatitis, 8.3 +/- 2.9 micrograms/ml in chronic active hepatitis, 7.8 +/- 2.9 micrograms/ml in liver cirrhosis and 8.2 +/- 2.1 micrograms/ml in hepatocellular carcinoma with cirrhosis. The percent collagen-binding vitronectin to total plasma vitronectin was 2.2 +/- 0.8% in the controls, 3.9 +/- 2.2% in chronic persistent hepatitis, 3.9 +/- 1.2% in chronic active hepatitis, 5.8 +/- 3.3% in liver cirrhosis and 4.1 +/- 1.2% in hepatocellular carcinoma with cirrhosis. The plasma collagen-binding vitronectin also correlated with the serum levels of 7S collagen and hyaluronic acid. These findings suggest that vitronectin may play an important role in the progression of liver disease and/or in hepatic fibrosis through its collagen-binding domain.

Aged↗

PubMed1992

Heat and autoclave resistance of cell-spreading activity of vitronectin.

We have investigated the heat- and autoclave-resistant properties of the cell-spreading activity of vitronectin, a cell-spreading glycoprotein in animal blood plasma. Vitronectin heated at 100 degrees C for 10 min or autoclaved at 121 degrees C at 1.2 kg/cm2 for 20 min retained the same cell-spreading activity as native vitronectin. In contrast, fibronectin and type-I collagen treated in the same way lost their activity almost completely. GRGDSP remarkably inhibited the cell-spreading activity of native, heated and autoclaved vitronectins. GRGESP did not inhibit the activity of native vitronectin, but, unexpectedly, partially inhibited the activity of both heated and autoclaved vitronectins. In SDS-polyacrylamide gel analysis under reducing conditions, vitronectin heated at 100 degrees C migrated mainly as a monomer, but autoclaved vitronectin migrated at both the top and front of the gel instead of at the position of the monomer. The change in molecular size during the heat- and autoclave treatments was partially prevented by adding 10 mM dithiothreitol or 2% 2-mercaptoethanol to the protein solution.

Amino Acid Sequence↗

PubMed1998

Ultrastructural localization and biochemical characterization of vitronectin in developing rat bone.

This study has used light and electron microscope immunohistochemical and biochemical methods to localize and characterize vitronectin in early bone formation of developing rat mandible with rabbit antimurine vitronectin IgG. Developing jaws of foetuses were collected at embryonic day 15 (day 15) to day 18 from pregnant Wistar rats. After aldehyde fixation, specimens with and without osmium post-fixation were dehydrated and embedded in paraffin, Spurr's resin or LR gold resin for morphological and immunohistochemical examinations. At the light microscope level, in day 15 samples, positive vitronectin immunostaining was observed in small elongated areas of intercellular matrix and osteoblasts. Concomitant with initiation of matrix mineralization at day 16, vitronectin staining was similarly observed in small elongated areas containing intercellular matrix and osteoblasts but not clearly detected in fully mineralized bone matrix. The same staining profile was observed at days 17 and 18. At the ultrastructural level, immunogold particles were clearly detected over unmineralized matrix and cisterns of the rough-surfaced endoplasmic reticulum and the Golgi apparatus of osteoblasts as well as over demineralized bone matrix at day 16-18. In order to assess the presence of vitronectin in the mineral phase, mineral-binding bone proteins were extracted from fresh day 18 specimens using a three-step technique: 4M guanidine HCl (G1 extract), aqueous EDTA without guanidine HCl (E extract), followed by guanidine HCl. Subsequent Western blot analysis of sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis revealed that the antibodies produced only a single band at an M(r) of approximately 73000 in both G1 and E extracts, indicating the presence of vitronectin in the mineralized bone matrix. These results indicate that, at the onset of bone formation, osteoblasts synthesize and release vitronectin, which is subsequently incorporated into the bone matrix and becomes a specific component of bone tissues. The observation of vitronectin in these critical stages of bone formation suggests that it may be involved in the regulation of bone formation.

Animals↗

PubMed2000

Vitronectin deficiency is associated with increased wound fibrinolysis and decreased microvascular angiogenesis in mice.

BACKGROUND: Vitronectin has several putative functions including regulating hemostasis, cell adhesion, and cell migration. However, the targeted deletion of vitronectin in mice results in normal development and normal coagulation parameters. To determine whether vitronectin may be necessary for nondevelopmental processes, we examined the response to tissue injury in vitronectin-null mice. METHODS: We examined wound healing in control and vitronectin-null mice by healing rate, zymography, reverse zymography, and Western blots. RESULTS: We found that dermal wound healing was slightly delayed in mice lacking vitronectin. More importantly, we found extensive areas of delayed hemorrhage near the sprouting tips of microvessels between days 7 and 14, which temporally coincided with increased urokinase-type plasminogen activator and tissue-type plasminogen activator activity by zymography. Though Western blots confirmed the presence of plasminogen activator inhibitor-1 protein throughout wound repair and reverse zymograms showed decreased plasminogen activator inhibitor-1 activity between days 7 and 14. CONCLUSIONS: Loss of vitronectin in mice was associated with changes in the fibrinolytic balance, and this may have led to focal sites of delayed hemorrhage. The mechanism that resulted in decreased angiogenesis and the formation of larger blood vessels in response to tissue injury remains unknown. This study suggests that vitronectin may have several distinct functions that are not required for normal development but are manifested in response to tissue injury.

Animals↗

PubMed1996

Characterization of the denaturation and renaturation of human plasma vitronectin. I. Biophysical characterization of protein unfolding and multimerization.

Upon treatment with denaturing agents, vitronectin has been observed to exhibit conformational alterations which are similar to the structural changes detected when vitronectin binds the thrombin-antithrombin complex or associates with the terminal attack complex of complement. Denaturation and renaturation of vitronectin isolated from human plasma were characterized by changes in intrinsic fluorescence. Unfolding by chemical denaturants was irreversible and accompanied by self-association of the protein to form vitronectin multimers. Self-association was evaluated by equilibrium analytical ultracentrifugation which demonstrated that multimers form only during the refolding process after removal of denaturant, that multimeric vitronectin dissociates to constituent subunits readily upon treatment with chemical denaturant, and that intermolecular disulfide cross-linking occurs primarily at the dimer level among a subset of constituent vitronectin subunits within the multimer. The monomeric form of vitronectin isolated from human plasma partially unfolds at intermediate concentrations of denaturant to an altered conformation with a high propensity to associate into multimers. Folding of vitronectin in vivo appears to be regulated by partitioning of folding intermediates toward either of two conformations, one that exists as a stable monomer and another that associates into a multimeric form.

Chromatography, High Pressure Liquid↗

PubMed1997

Native and multimeric vitronectin exhibit similar affinity for heparin. Differences in heparin binding properties induced upon denaturation are due to self-association into a multivalent form.

For many years, the concept that the heparin-binding sequence is sequestered within vitronectin and exposed upon denaturation of the protein has guided experimental design and interpretation of related structure-function studies on the protein. To evaluate binding of heparin to both native and denatured/renatured vitronectin, methods for monitoring binding in solution have been developed. A fluorescence method based on changes in an extrinsic probe attached to heparin has been used to evaluate heparin binding to native and denatured/renatured vitronectin. This approach indicates that there are not major differences in intrinsic heparin-binding affinities between native and renatured protein and invalidate the currently accepted model for a cryptic heparin-binding sequence in the protein. Denaturation and renaturation of vitronectin under near physiological solution conditions is accompanied invariably by self-association of the protein into a multimeric form (Zhuang, P., Blackburn, M. N., and Peterson, C. B. (1996) J. Biol. Chem. 271, 14323-14332), resulting in exposure of multiple heparin-binding sites on the surface of the oligomer. On the basis of the binding data from solution studies and interaction of the native monomer and the denatured multimeric form of vitronectin with a heparin column, along with evaluation of the ionic strength dependence of heparin binding to these vitronectin forms in solution, an alternative model is favored to account for the altered heparin binding properties of vitronectin associated with denaturation of the protein. This model proposes that multivalent interactions between heparin and multimeric vitronectin are responsible for differences in heparin affinity chromatography and ionic strength dependence compared with the native protein.

Animals↗

PubMed1999

Orientation of heparin-binding sites in native vitronectin. Analyses of ligand binding to the primary glycosaminoglycan-binding site indicate that putative secondary sites are not functional.

A primary heparin-binding site in vitronectin has been localized to a cluster of cationic residues near the C terminus of the protein. More recently, secondary binding sites have been proposed. In order to investigate whether the binding site originally identified on vitronectin functions as an exclusive and independent heparin-binding domain, solution binding methods have been used in combination with NMR and recombinant approaches to evaluate ligand binding to the primary site. Evaluation of the ionic strength dependence of heparin binding to vitronectin according to classical linkage theory indicates that a single ionic bond is prominent. It had been previously shown that chemical modification of vitronectin using an arginine-reactive probe results in a significant reduction in heparin binding (Gibson, A., Baburaj, K., Day, D. E., Verhamme, I. , Shore, J. D., and Peterson, C. B. (1997) J. Biol. Chem. 272, 5112-5121). The label has now been localized to arginine residues within the cyanogen bromide fragment-(341-380) that contains the primary heparin-binding site on vitronectin. One- and two-dimensional NMR on model peptides based on this primary heparin-binding site indicate that an arginine residue participates in the ionic interaction and that other nonionic interactions may be involved in forming a complex with heparin. A recombinant polypeptide corresponding to the C-terminal 129 amino acids of vitronectin exhibits heparin-binding affinity that is comparable to that of full-length vitronectin and is equally effective at neutralizing heparin anticoagulant activity. Results from this broad experimental approach argue that the behavior of the primary site is sufficient to account for the heparin binding activity of vitronectin and support an exposed orientation for the site in the structure of the native protein.

Amino Acid Sequence↗

PubMed2001

Mechanisms of enhanced osteoblast adhesion on nanophase alumina involve vitronectin.

The role, including concentration, conformation, and bioactivity, of adsorbed vitronectin in enhancing osteoblast adhesion on nanophase alumina was investigated in the present study. Vitronectin adsorbed in a competitive environment in the highest concentration on nanophase alumina compared to conventional alumina. Enhanced adsorption of vitronectin on nanophase alumina was possibly due to decreased adsorption of apolipoprotein A-I and/or increased adsorption of calcium on nanophase alumina. In a novel manner, the present study utilized surface-enhanced Raman scattering (SERS) to determine the conformation of vitronectin adsorbed on nanophase alumina. These results provided the first evidence of increased unfolding of vitronectin adsorbed on nanophase alumina. Increased adsorption of calcium on nanophase alumina may affect the conformation of adsorbed vitronectin specifically to promote unfolding of the macromolecule to expose cell-adhesive epitopes recognized by specific cell-membrane receptors. Results of the present study also provided evidence of dose-dependent inhibition of osteoblast adhesion on nanophase alumina pretreated with vitronectin following preincubation (and thus blocking respective cell-membrane receptors) with either Arginine-Glycine-Aspartic Acid-Serine (RGDS) or Lysine-Arginine-Serine-Arginine (KRSR). These events, namely, enhanced vitronectin adsorption, comformation, and bioactivity, may explain the increased osteoblast adhesion on nanophase alumina.

Adsorption↗

PubMed2002

Interaction of vitronectin with Haemophilus influenzae.

Eight strains of Haemophilus influenzae were tested for binding to human vitronectin. All strains adhered to vitronectin-coated glass slides but no binding was detected using soluble vitronectin, suggesting that surface association of vitronectin is a prerequisite. Vitronectin binding was not likely to be mediated by fimbriae as non-fimbriated and fimbriated isogenic strains adhered equally. Adhesion could be blocked by heparin, which is also known to block vitronectin binding to Staphylococcus aureus. However, no blocking was achieved with sialic acid-rich glycoproteins such as fetuin and mucin contrasting with Helicobacter pylori for which sialic acid seems to play an important role. With Streptococcus pneumoniae binding was detected both with soluble and surface-associated vitronectin and could not be blocked by heparin. Our results suggest that H. influenzae, Streptococcus pneumoniae and Helicobacter pylori all use distinct modes to interact with vitronectin.

Bacterial Adhesion↗