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PubMed1995

[Vitronectin in children with renal disease--2. Examination of urinary vitronectin excretion].

Urinary vitronectin excretion was measured by ELISA in healthy and various renal diseases children. In 36 healthy children, urinary vitronectin was excreted at low levels in the range of 0-2.71 (0.187 +/- 0.655) micrograms/g.Cre. Urinary Vitronectin and the positive ratio in various renal diseases were as follows: IgA nephropathy: 0-59.22 (3.420 +/- 9.180) micrograms/g.Cre, 41%; Henoch-Schönlein purpura nephritis: 0-118.40 (19.619 +/- 31.713) micrograms/g.Cre, 53%; membranous nephropathy: 0-2.76 (0.595 +/- 0.885) micrograms/g.Cre, 18%; membrano-proliferative glomerulonephritis: 0-11.00 (1.888 +/- 3.078) micrograms/g.Cre, 33%; acute glomerulonephritis: 0.07-0.84 (0.456 +/- 0.317) microgram/g.Cre, 0%; Alport's syndrome: 0.81-112.12 (32.378 +/- 44.038) micrograms/g.Cre 67%; focal segmental glomerulosclerosis: 0.30-31.86 (12.070 +/- 17.241) micrograms/g.Cre, 67%; idiopathic nephrotic syndrome with proteinuria: 0-2.89 (0.551 +/- 1.064) micrograms/g.Cre 17%; idiopathic nephrotic syndrome in remission: 0-0.97 (0.258 +/- 0.372) microgram/g.Cre 0%, respectively. In patients with chronic renal failure, urinary vitronectin was excreted at high levels in the range of 2.15-446.08 (118.696 +/- 144.338) micrograms/g.Cre and the positive ratio of urinary vitronectin was 100%. In IgA nephropathy, Henoch-Schönlein purpura nephritis, membrano-proliferative glomerulonephritis, Alport's syndrome, focal segmental glomerulosclerosis and chronic renal failure, the positive ratio of urinary vitronectin was higher than in healthy children, but in membranous nephropathy, acute glomerulonephritis, idiopathic nephrotic syndrome with proteinuria and in remission, the positive ratio of urinary vitronectin was not significantly different from that of healthy children.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1990

Specific binding of plasminogen to vitronectin. Evidence for a modulatory role of vitronectin on fibrin(ogen)-induced plasmin formation by tissue plasminogen activator.

Vitronectin immobilized onto polystyrene microtiter wells was demonstrated to specifically bind plasminogen in a concentration-dependent manner, yielding an estimated KD = 0.4 microM. Heparin only moderately interfered with the vitronectin-plasminogen interaction, whereas high concentrations of 6-amino-hexanoic acid inhibited binding. Utilizing a ligand-blotting procedure in which plasminogen was reacted with proteolytic fragments of vitronectin, transblotted onto nitrocellulose, the plasminogen-binding site of vitronectin was localized to the heparin-binding domain of the adhesive protein. Moreover, vitronectin was found to inhibit in a dose-dependent fashion the fibrin(ogen)-induced activation of plasminogen by tissue plasminogen activator. These results provide the first evidence for a novel vitronectin-mediated control of plasminogen activation potentially relevant for directional clot-lysis and plasmin-dependent proteolysis in extracellular matrices.

Electrophoresis, Polyacrylamide Gel↗

PubMed1994

Low levels of vitronectin and clusterin in acute meningococcal disease are closely associated with formation of the terminal-complement complex and the vitronectin-thrombin-antithrombin complex.

Patients with terminal complement deficiencies and thus impaired lytic efficiency have a highly increased likelihood of contracting invasive meningococcal infections but generally experience a mild disease course. Deficiencies of lysis inhibitors might therefore be associated with severe disease. We have quantified the complement lysis inhibitors vitronectin and clusterin, as well as complexes containing the proteins, in plasma from patients with acute meningococcal disease. At hospital admission, the median vitronectin concentrations were 0.10 (range, 0.04 to 0.17) g/liter in 10 septic patients and 0.19 (0.09 to 0.47) g/liter in 14 nonseptic patients (P = 0.001). The corresponding clusterin concentrations were 0.09 (0.01 to 0.13) and 0.14 (0.06 to 0.29) g/liter (P = 0.005). The vitronectin-thrombin-antithrombin complex concentration was 1.8 (0.22 to 35.6) arbitrary units (AU)/ml in septic patients, but the complex was not detectable in most nonseptic patients (< 0.10 to 0.16 AU/ml) (P < 0.0001). The corresponding levels of the terminal complement complex (contains vitronectin and clusterin) were 4.4 (3.6 to 20.1) and 2.6 (1.6 to 4.7) AU/ml (P = 0.0005). We found no evidence of constitutively low levels of vitronectin or clusterin in patients contracting meningococcal disease. The low levels of the proteins may partly be explained by hemodilution, extravasation, and increased consumption due to incorporation into complexes which are quickly removed from circulation.

Adolescent↗

PubMed1992

Platelets and vitronectin: immunocytochemical localization and platelet interaction with exogenously added vitronectin.

Vitronectin stores were localized in human platelets by immunofluorescence, confocal laser microscopy, and immunoelectron microscopy. In ultrathin cryosections, the immunogold labelling was mainly observed in the alpha-granules, although occasional immunolabelling of the platelet surface was present. The interaction between thrombin-stimulated platelets and exogenously added vitronectin was also explored. This vitronectin had been purified by heparin-affinity chromatography. Binding of vitronectin to thrombin-stimulated platelets was demonstrated by flow cytometry. The immunoelectron microscopical studies revealed that this binding was mainly restricted to clumps of released alpha-granular material on the platelet surface. The possible significance of the interaction between exogenous vitronectin and released platelet proteins is discussed.

Amino Acid Sequence↗

PubMed1990

The integrin beta 1 subunit associates with the vitronectin receptor alpha v subunit to form a novel vitronectin receptor in a human embryonic kidney cell line.

We describe a novel integrin heterodimer on the surface of the human embryonic kidney cell line 293. This receptor is comprised of alpha v and beta 1 subunits, each of which has been previously found in association with other integrin subunits. This alpha v.beta 1 complex was identified as the predominant vitronectin receptor (VnR) on the surface of 293 cells by immunoprecipitation with antibodies raised against the alpha v subunit. Polymerase chain reaction analysis detected mRNAs for alpha v and beta 1 subunits while no evidence was obtained for beta 2, beta 3, or alpha IIb integrin subunit mRNA. Immunoprecipitation of surface-iodinated proteins with antibodies to alpha v gave bands of 150 and 120 kDa. The 120-kDa band reacted with antibodies to beta 1 in immunoblotting experiments. 293 cells adhere to vitronectin, fibronectin, laminin, and collagen IV, while von Willebrand factor and fibrinogen, known ligands of the VnR (alpha v.beta 3), did not support adhesion. A polyclonal antibody directed against both subunits of the VnR (alpha v, beta 3) inhibits attachment of 293 cells to vitronectin but not to other adhesive proteins. A beta 1-specific monoclonal inhibited attachment to fibronectin, laminin, and collagen IV, known ligands of beta 1 integrins, as well as vitronectin. This novel (alpha v. beta 1) VnR thus appears to mediate cell adhesion exclusively to vitronectin, in contrast to previously described VnRs which have multiple ligands.

Antibodies↗

PubMed1991

Vitronectin and proliferative intraocular disorders. I. A colocalisation study of the serum spreading factor, vitronectin, and fibronectin in traction membranes from patients with proliferative vitreoretinopathy.

The presence of a scaffold for cellular spreading and proliferation is a precondition for the development of traction membranes in proliferative vitreoretinopathy (PVR). This study shows the presence of the serum spreading factor, vitronectin, in the extracellular matrix of periretinal membranes removed during vitreoretinal surgery. By means of a double label immunofluorescence protocol, a partial colocalisation of vitronectin with fibronectin at the magnification of light microscopy can be detected. Fibronectin is a high-molecular glycoprotein with multiple biological functions including the mediation of cell attachment and migration. Both proteins share a special cell recognition site which could be a target for experimental pharmacological approaches to PVR. Preliminary studies of vitreous aspirates using electrophoresis and Western blotting indicate that vitronectin may play a more important role in post-traumatic PVR as compared to PVR following rhegmatogenous retinal detachment.

Blotting, Western↗

PubMed1991

Vitronectin and proliferative intraocular disorders. II. Expression of cell surface receptors for fibronectin and vitronectin in periretinal membranes.

Several cell types participate in the formation of vitreoretinal traction membranes in proliferative intraocular disorders. The communication between these cells involves hormones, growth factors, and the interaction with extracellular matrix molecules. We have previously demonstrated a partial colocalisation of two potent mediators of cell attachment, fibronectin and vitronectin, in periretinal membranes from patients with proliferative vitreoretinopathy (PVR). We found a similar pattern of vitronectin and fibronectin deposition in proliferative diabetic retinopathy (PDR) (n = 6). Now we show the expression of the corresponding cell surface receptors, integrins, for fibronectin and vitronectin by proliferating cells in 22 periretinal membranes, including traumatic (n = 8) and idiopathic (n = 8) PVR as well as PDR membranes (n = 6). Integrins are membrane receptors for extracellular matrix macromolecules which are involved in such basic biological phenomena as embryogenesis and metastasis. Future studies on the pathogenesis of vitreoretinal proliferation will have to focus on the initiation, maintenance, and regulation of this intercellular communication network involving attachment proteins and integrins.

Diabetic Retinopathy↗

PubMed1997

Nonimmune phagocytosis of liposomes by rat alveolar macrophages is enhanced by vitronectin and is vitronectin-receptor mediated.

Pulmonary alveolar macrophages (AMs) engulf diverse materials. The mechanisms allowing AMs to recognize, bind, and phagocytose these materials are poorly understood. To test the hypothesis that the adhesive glycoprotein vitronectin (Vn) acts as a nonimmune opsonin, we studied AM-Vn binding and AM phagocytosis of fluorescent liposomes under the following conditions: (1) pretreatment of AMs with Vn, followed by incubation of AMs with liposomes containing increased amounts of Vn; (2) inhibition of phagocytosis by gly-arg-gly-asp-ser (RGD) and gly-pen-gly-arg-gly-asp-ser-pro-cys-ala (GPen); and (3) antibody blockade of the alpha(v)beta3 vitronectin receptor (VnR). Pretreatment of AMs with 0.1, 1, and 2 microM Vn progressively enhanced AM-Vn binding from 23,622 +/- 3,328 cpm to 40,847 +/- 6,530 cpm, 57,149 +/- 2,789 cpm, and 124,852 +/- 42,930 cpm, respectively (P < 0.05). AM pretreatment also increased phagocytosis of Vn-enriched liposomes, but not empty liposomes (20.7 +/- 0.4 liposomes/cell versus 11.5 +/- 0.5 liposomes/cell, P < 0.05). Moreover, increased concentrations of Vn in liposomes progressively increased phagocytic activity (3.7 +/- 0.3, 6.5 +/- 0.2, 11.5 +/- 0.5, and 16.5 +/- 0.6 liposomes/cell with 0.01, 0.1, and 1 microM Vn, respectively, P < 0.05). RGD inhibited Vn-enhanced phagocytosis (8.1 +/- 0.4 liposomes/cell to 3.4 +/- 0.2, 2.4 +/- 0.4, and 2.2 +/- 0.2 liposomes/cell with 0.02, 0.2, and 2 mM RGD, respectively, P < 0.05), as did GPen (4.7 +/- 0.8 liposomes/cell versus control = 10.9 +/- 1.5 liposomes/cell, P < 0.05) and anti-VnR antibody (3.3 +/- 0.4 liposomes/cell versus control = 8.9 +/- 1.7 liposomes/cell, P < 0.05). We conclude that AMs employ Vn as a nonimmune opsonin to enhance the efficiency of phagocytosis.

Animals↗

PubMed1992

Binding of vitronectin-thrombin-antithrombin III complex to human endothelial cells is mediated by the heparin binding site of vitronectin.

The interaction of vitronectin-thrombin-antithrombin III (VN.TAT) complex with endothelial cells (EC) was investigated. Binding was specific and time- and concentration-dependent. Kinetics revealed an apparent dissociation constant of 16 nM and 1.7 x 10(5) binding sites/endothelial cell. The binding determinant of the ternary complex was located on the VN moiety. Since the association of VN to TAT adds its specific properties to the VN.TAT complex, the involvement of the heparin binding domain and the cell attachment site of VN was investigated. Neither addition of RGD peptide nor blocking of the vitronectin receptor with a monoclonal antibody interfered with VN.TAT binding to EC. Addition of heparin, a VN-derived peptide comprising two heparin binding consensus sequences or a monoclonal antibody directed against the heparin binding domain on VN, completely inhibited VN.TAT binding to EC. These results indicate that the interaction is mediated through the heparin binding domain of VN. Digestion of heparan sulfate proteoglycans resulted in a decrease of VN.TAT binding to EC, indicating the involvement of heparin-like structures on the EC surface. Our findings point to an unrecognized mechanism by which VN may act as scavenger in order to enhance the clearance of end products of the clotting system via binding of the ternary VN.TAT complex to the luminal surface of EC.

Amino Acid Sequence↗

PubMed1989

Biogenesis of the vitronectin receptor in human endothelial cell: evidence that the vitronectin receptor and GPIIb-IIIa are synthesized by a common mechanism.

Human endothelial cells express a membrane glycoprotein alpha beta heterodimer similar to the human platelet glycoprotein IIb-IIIa complex (GPIIb-IIIa). This noncovalently associated complex is the vitronectin receptor (VNR). These two receptors belong to the cytoadhesin family and share the same beta subunit. They express different recognition specificities: platelet GPIIb-IIIa is a receptor for fibrinogen, fibronectin, and von Willebrand factor (vWF), whereas VNR is a receptor for vitronectin, and is possibly a receptor for fibrinogen and vWF. We analyzed the biosynthesis of the endothelial cell VNR. Our data show that VNR alpha is a two-chain protein which is biosynthesized as a single-chain precursor: the pro-VNR alpha. Pro-VNR alpha forms a complex with VNR beta, and this association occurs prior to the Golgi-mediated processing of the oligosaccharide side chains. Mature VNR beta is glycosylated by not fully processed oligosaccharide side chains because it remains endoglycosidase H (endo H) sensitive, even when the complex is expressed on the cell surface. This characteristic appears as a common feature for the members of the cytoadhesin family. These results indicate that although VNR and GPIIb-IIIa are biosynthesized in different cells, their expression is controlled by similar mechanisms, providing further support for the concept that the cytoadhesin family constitutes a distinct group of adhesion receptors.

Cells, Cultured↗

PubMed1996

Expressions of very late antigen-6 and vitronectin receptor, and their interactions to laminin and vitronectin during tonsillar B-cell activation.

This study examined the expressions of a-subunits of very late antigen-6 (VLA-6; alpha 6) and vitronectin receptor (VNR; alpha V) on tonsillar B cells and interactions between those integrins and their respective ligands, laminin (LM) and vitronectin (VN). alpha 6 and alpha V were expressed on about 30 to 40% of tonsillar B cells. When purified tonsillar B cells were separated by a discontinuous Percoll gradient, the number of alpha 6- and alpha V-positive cells decreased as the cell density went down, while the number of activated cells went up. After in vitro activation of tonsillar B cells by Staphylococcus aureus Cowan I strain (SAC), the expressions of alpha 6 and alpha V and their adhesiveness to LM or VN decreased significantly. Increased proliferation of B cells was observed when tonsillar B cells were cultured with immobilized LM or VN. The results of immunohistological staining showed VLA-6, VNR, LM and VN in the follicular area. These results suggest that the expressions of VLA-6 and VNR on tonsillar B cells may be decreased during B cell activation, and the interaction between VLA-6, VNR, and LM, VN may give a costimulatory effect on B cell activation in the follicular area of the tonsil.

Antibodies, Monoclonal↗

PubMed2002

Vitronectin is up-regulated after vascular injury and vitronectin blockade prevents neointima formation.

OBJECTIVE: Smooth muscle cell (SMC) migration involves interactions with extracellular matrix (ECM) and is an important process in response to arterial wall injury. We investigated the expression and the functional role of vitronectin (VN) in the response after vascular injury. METHODS: VN and alpha v beta 3/beta 5 integrin expressions were investigated after balloon carotid injury of Sprague-Dawley rats. Adventitial delivery of blocking antibodies to VN, alpha v beta 5 and beta 3 integrins were performed to assess their roles in neointima formation. In vitro, migration assays were carried out on human SMC. RESULTS: Immunohistochemistry and in situ hybridization for VN showed an upregulation of VN during the early time points of intima formation. alpha v beta 3/beta 5 integrins expression correlated with VN expression. After 7 days, blocking antibodies to VN, alpha v beta 5 and beta 3 induced a significant decrease on intimal area associated with a decrease in intimal cell counts. A slight decrease in intimal cell proliferation without any effect on apoptosis was observed after VN blockade. In vitro, migrating SMC strongly expressed VN after injury and neutralizing anti-VN antibody inhibited SMC migration. Blocking experiment with anti-alpha v beta 5 and -alpha v beta 3 integrin antibodies showed that not only VN-alpha v beta 3 but also VN-alpha v beta 5 interactions are required for SMC migration. CONCLUSION: This study characterizes the VN-ECM interaction in SMC and supports the role of VN in mediating SMC migration and neointimal formation in response to injury.

Adult↗

PubMed1995

Vitronectin and integrin vitronectin receptor localization in multiple sclerosis lesions.

Vitronectin (Vn) is a multifunctional plasma and extracellular matrix glycoprotein involved in cell attachment, coagulation, phagocytosis, and the protection of bystander cells from complement- and T cell-mediated lysis. To determine where Vn is localized and where cells expressing integrin Vn receptors may recognize it in central nervous system (CNS) lesions of multiple sclerosis (MS), CNS tissue samples were immunostained for Vn and the alphav, beta 1, and beta 3 integrin Vn receptor subunits. By light and electron microscopy, Vn was localized within dystrophic, demyelinated axons in active but not chronic lesions, normal or other neurologic disease controls. This localization is distinct from that of other plasma proteins in MS lesions and it differs from the pattern of neuron cell body localization found in other conditions. Microvascular Vn was increased and small numbers of reactive astrocytes were also Vn-positive in active plaques. Endothelial cell expression of the alpha v subunit was increased over controls and that of the beta 1 subunit was decreased whereas both the alpha v and beta 1 subunits were prominently expressed on macrophages and glia in active lesions. The beta 3 integrin subunit was expressed on platelets within and around vessels and was more prominent on endothelial cells in active plaques. The precise functions of Vn in situ are not presently known. These results indicate, however, that the regulation of expression of integrin Vn receptors is complex and that Vn may be recognized and have multiple functions in different microanatomic sites as MS lesions evolve. Intravascular Vn could participate in clotting, thereby contributing to leukocyte extravasation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1996

Type 1 plasminogen activator inhibitor induces multimerization of plasma vitronectin. A suggested mechanism for the generation of the tissue form of vitronectin in vivo.

The conformation and degree of multimerization of vitronectin (Vn) appears to be of critical importance for its functions, but little is known about the underlying mechanisms that control Vn multimerization. We report that Vn secreted by cultured hepatoma cells is present as a mixture of monomeric and multimeric forms. A single protein of Mr 45,000 co-purified with hepatoma cell-derived Vn, which was immunologically identified as type 1 plasminogen activator inhibitor (PAI-1). The possibility that PAI-1 may modulate Vn multimerization was investigated. The addition of active PAI-1 to unfractionated plasma containing Vn monomers resulted in the formation of covalently and noncovalently associated Vn multimers and expression of conformationally sensitive epitopes. In contrast, inactive forms of PAI-1 did not efficiently induce Vn multimerization and conformational change. Gel filtration analysis revealed that Vn remained multimeric after dissociation from PAI-1. Vn multimers were also assembled using purified monomeric Vn and PAI-1, suggesting that a plasma cofactor was not required to induce Vn multimerization. This study provides insights into physiological mechanism responsible for the generation of homomultimeric Vn, a multimeric form of Vn that is not in complex with other proteins and which expresses a functional repertoire distinct from that of plasma Vn.

Biopolymers↗

PubMed2004

Fibrin-incorporated vitronectin is involved in platelet adhesion and thrombus formation through homotypic interactions with platelet-associated vitronectin.

When a blood clot is formed, vitronectin (VN) is incorporated. Here we studied the consequence of VN incorporation for platelet interactions under flow. Perfusion of whole blood over a fibrin network, formed from purified fibrinogen, resulted in approximately 20% surface coverage with blood platelets. Incorporation of purified multimeric VN into the fibrin network resulted in a 2-fold increase in surface coverage with platelets and in enhancement of platelet aggregate formation. A human monoclonal antibody (huMab VN18), directed against the multimeric form of VN, inhibited platelet adhesion to the combined fibrin/VN matrix to the level of adhesion on fibrin alone. This inhibition was also shown when whole blood was perfused over a plasma-derived clot. Surprisingly, the inhibitory action of the antibody was not directed toward VN incorporated into the fibrin network but toward VN released from the platelets. We conclude that VN-potentiated platelet-clot interaction requires VN in the clot and multimeric VN bound to the platelet surface. Our results provide evidence that homotypic VN interactions contribute to platelet adhesion and aggregation to a blood clot. This report demonstrates for the first time that self-assembly of VN may provide a physiologically relevant contribution to platelet aggregation on a blood clot.

Antibodies, Monoclonal↗

PubMed1992

Mapping of binding sites for heparin, plasminogen activator inhibitor-1, and plasminogen to vitronectin's heparin-binding region reveals a novel vitronectin-dependent feedback mechanism for the control of plasmin formation.

Vitronectin (VN) has been implicated as a major matrix-associated regulator component of plasminogen activation by serving as a potent stabilizing cofactor of plasminogen activator inhibitor-1 (PAI-1). The direct binding of heparin, plasminogen as well as PAI-1 in its latent and active form to immobilized VN was studied in the absence or presence of competitors. Monoclonal antibodies against the carboxyl-terminal portion of VN inhibited both PAI-1 and plasminogen binding, whereas heparin, heparan sulfate with a high degree of sulfation, or dextran sulfate interfered with PAI-1 binding (KD = 20 nM) only. Utilizing synthetic peptides encompassing overlapping sequences of the heparin-binding domain of VN, adjacent heparin and PAI-1-binding sites were localized within the sequence 348-370 of VN. Although a number of other serine protease inhibitors which do not form binary complexes with VN contain a reactive-site Ser at their P1'-position, a reactive-site P1' mutant of PAI-1 (Met----Ser) showed comparable if not increased binding to VN. Binding of Lys-plasminogen and active-site-blocked plasmin was at least 10-fold higher in affinity (KD = 85-100 nM) compared to Glu-plasminogen (KD approximately 1 microM) and could be inhibited by lysine analogs but not by glycosaminoglycans or PAI-1, indicating that heteropolar plasmin(ogen) binding of VN occurs to an adjacent segment upstream to the heparin and PAI-1-binding sites. This contention was further supported in binding studies with plasmin-modified VN which lost both heparin and PAI-1 binding but exhibited 2-3-fold higher capacity to bind plasminogen. The essential plasmin(ogen)-binding site was mapped by ligand blot analysis to the carboxyl-terminal portion of proteolytically trimmed VN (M(r) = 61,000). Moreover, treatment of the extracellular matrix of human umbilical vein endothelial cells with plasmin resulted in partial degradation of matrix-associated VN and concomitant release of PAI-1, but increased the ability of the matrix by about 2-fold to bind plasminogen. These results are indicative of differential interactions of VN with components of the plasminogen activation system, whereby plasmin itself may provoke the switch of VN from an anti-fibrinolytic into a pro-fibrinolytic cofactor. This process reflects a novel role for the adhesive protein and its degradation product(s) in the possible feedback regulation of localized plasmin formation at extracellular sites.

Amino Acid Sequence↗

PubMed1990

Highly sulfated glycosaminoglycans augment the cross-linking of vitronectin by guinea pig liver transglutaminase. Functional studies of the cross-linked vitronectin multimers.

Vitronectin (VN) is an adhesive glycoprotein with roles in the complement, coagulation, and immune systems. Many of the functions of VN are mediated by a glycosaminoglycan binding site, near its carboxyl-terminal end. In this paper, we show that the highly sulfated glycosaminoglycans (GAGs), dextran sulfate, pentosan polysulfate, and fucoidan effectively augment [14C]putrescine incorporation into VN and cross-linking of VN into high molecular multimers by guinea pig liver transglutaminase (TG). Other GAGs including heparin, low molecular weight heparin, dermatan sulfate, keratan sulfate, and the nonsulfated dextrans were ineffective in accelerating these reactions. Dextran sulfate of average molecular mass 500 kDa was more effective than dextran sulfate of average molecular mass 5 kDa, supporting a template mechanism of action of the GAGs, in which VN molecules align on the GAG in a conformation suitable for cross-linking. The VN multimers catalyzed by TG retained functional activity in binding [3H]heparin, platelets, and plasminogen activator inhibitor type-1 (PAI-1). [3H]Heparin bound selectively to the 65-kDa monomeric band of VN and to the multimers derived from this band. PAI-1, however, bound equally to both the 75- and 65-kDa monomeric forms of VN, suggesting that the PAI-1 binding site on VN is distinct from the GAG binding site. The interaction of GAGs with the TG-catalyzed cross-linking of VN may facilitate studies of VN structure-function relationships.

Animals↗

PubMed1991

[Changes in plasma vitronectin, fibronectin, and serum laminin P1 levels and immunohistochemical study of vitronectin in the liver of patients with chronic liver diseases].

Vitronectin (VN), fibronectin (FN) and laminin (LM), which are known to be important glycoproteins in cell attachment, are produced by such liver cells as hepatocytes, Kupffer cells endothelial cells and Ito cells. In this study, the levels of plasma VN, FN and serum LM P1 in patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma accompanied with cirrhosis were examined and compared with those in normal subjects. Plasma VN levels in patients with chronic hepatitis, compensated cirrhosis and decompensated cirrhosis were less than that in normal subjects. As hepatic dysfunction deteriorated, plasma VN level decreased in chronic liver diseases. Plasma FN levels in patients with compensated and decompensated cirrhosis were also less than that of patients with chronic hepatitis, which was not significantly different from that of normal subjects. Plasma VN and FN levels in patients with hepatocellular carcinoma were similar to those in patients with compensated cirrhosis. Plasma VN and FN levels in patients with chronic liver diseases including hepatocellular carcinoma showed positive correlations with serum albumin content, cholinesterase activity, and normalized normo test value. On the other hand, serum LM P1 levels in patients with chronic hepatitis, compensated cirrhosis and decompensated cirrhosis were higher than that of normal subjects. As hepatic dysfunction deteriorated, serum LM P1 level increased in chronic liver diseases. Level of serum type IV collagen 7S, which is related to hepatic fibrosis, was similar to that of serum LM P1; serum LM P1 concentration in patients with chronic liver diseases showed a significant positive correlation with that of serum type IV collagen 7S. Immunolocalization of VN in liver tissue from patients with chronic hepatitis and cirrhosis was examined by the method of avidin-biotin-complex staining, and positive reaction was observed in enlarged portal tracts, central veins and fibrous septa. These results suggest that decreased levels of plasma VN and FN and increased level of serum LM P1 in patients with chronic liver diseases are related to hepatic dysfunction, and that changes in the levels of these glycoproteins involved in cell attachment are important in the development of hepatic fibrosis in patients with chronic liver diseases.

Adult↗