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PubMed2000

[The vitronectin anchors on placenta tissue of hypertensive pregnancy].

Using immunohistochemistry staining and Western-blot techniques, we detected the distribution and content of vitronectin antigen in placenta tissue of one case of hypertensive pregnancy in order to explore pathogenesis of the development of hypertensive pregnancy. The results were that vitronectin expressions on hypertensive pregnant placenta were obviously higher than those on normal placenta, which suggests that fibrin deposition on placenta tissue was associated with suppression of fibrinolysis.

Female↗
PubMed1991

[Vitronectin in normal human skin and in skin lesions].

Vitronectin (S-protein of complement, serum spreading factor) is a multifunctional glycoprotein present in human plasma and in the elastic tissue of various organs. It belongs to the group of adhesion proteins and is of importance in the terminal stages of both the coagulation and complement system and in fibrinolysis. In human skin it is localized on dermal elastic fibers and on pathologically altered elastic material (solar elastosis, pseudoxanthoma elasticum) as well as on keratin filament material such as keratin bodies in lichen planus or amyloid deposits in localized cutaneous amyloid. It is also found in the abnormally thickened cutaneous blood vessels in erythropoietic protoporphyria and porphyria cutanea tarda. Late-stage inhibition of the complement cascade in bullous disorders in which activation of the complement system is of pathogenetic significance may be an additional important function of vitronectin in skin diseases.

Blood Coagulation↗
PubMed1991

Endothelial cell damage by Walker carcinosarcoma cells is dependent on vitronectin receptor-mediated tumor cell adhesion.

The transport of cancer cells from blood vessels to extravascular tissue is a critical step in metastasis, where endothelial cells and the vascular basement membrane act as barriers to cell traffic. Because endothelial injury can facilitate the metastasis of intravascular cancer cells in vivo, the authors have studied in vitro the free-radical-mediated endothelial damage caused by the rat Walker 256 carcinosarcoma (W256) cell after stimulation with 10(-6) mol/l (molar) phorbol ester. Here the authors have examined the hypothesis that W256 cell-mediated endothelial injury is dependent on adhesion between the effector and target cells. Attachment of phorbol 12-myristate, 13-acetate (PMA)-stimulated W256 cells to endothelial monolayers was increased 1.8 +/- 0.1-fold and damage (3H-2-deoxyglucose release from labeled endothelium) 1.4 +/- 0.1-fold after 4-hour pretreatment of the endothelium with 10 ng/ml recombinant human interleukin-1 alpha (rIL-1 alpha). Under various assay conditions, the release of 3H-2-deoxyglucose correlated directly with tumor cell adhesion (r = 0.98, P less than 0.005). In the presence of a polyclonal anti-vitronectin receptor antiserum, adhesion of stimulated W256 cells to rIL-1 alpha-treated monolayers was inhibited by 39% +/- 2%, and 3H-2-deoxyglucose release was inhibited by 53% +/- 13%. Immunoblot analysis and immunofluorescence flow cytometry demonstrated that the endothelial cells but not the W256 cells expressed vitronectin receptor (VnR) on their cell surface. The surface expression of VnR by endothelial cells was increased 1.9 +/- 0.1-fold after 4 hours' incubation with rIL-1 alpha. The authors conclude that W256 cell-mediated endothelial damage is dependent on cell adhesion, which, in turn, is partly regulated by the expression of VnR on the endothelial cell surface.

Animals↗
PubMed1987

Biosynthetic and functional properties of an Arg-Gly-Asp-directed receptor involved in human melanoma cell attachment to vitronectin, fibrinogen, and von Willebrand factor.

M21 human melanoma cells express an Arg-Gly-Asp-directed adhesion receptor composed of noncovalently associated alpha and beta chains. To establish the structural and functional properties of this receptor on M21 human melanoma cells, stable variant cell lines were selected that express altered alpha chain levels. One of these variants, M21-L, fails to synthesize alpha chain protein or its mRNA, yet does produce normal levels of the beta chain. In these cells the beta chain does not reach the cell surface but rather accumulates within the cell. M21-L cells lacking the alpha chain are incapable of attaching to vitronectin, von Willebrand factor, fibrinogen, or an Arg-Gly-Asp-containing heptapeptide yet attach normally to fibronectin, whereas the unselected M21 cells attach to all of these adhesive proteins. In addition, a monoclonal antibody, LM609 generated to a functional site on the intact receptor, is capable of preventing M21 cell attachment to vitronectin, von Willebrand factor, fibrinogen, and the Arg-Gly-Asp peptide but not to fibronectin. Following a 2-min biosynthetic pulse-label, the newly synthesized alpha chain remains in free form for 5 min and then associates with previously synthesized beta chain present in an intracellular pool. Once oligomerization takes place, the receptor gains the capacity to recognize Arg-Gly-Asp, and at this time the epitope recognized by monoclonal antibody LM609 is formed.

Cell Adhesion↗
PubMed1989

Expression of the vitronectin receptor during embryonic development; an immunohistological study of the ontogeny of the osteoclast in the rabbit.

The development of the osteoclast during embryogenesis was studied in the rabbit by immunohistological techniques. Two monoclonal antibodies, 13C2 and 23C6, which react with the alpha-chain of the vitronectin receptor were used to define mono and multi-nucleate osteoclasts; being unreactive with other haemopoietic cells these antibodies could discriminate between osteoclasts and cells of the mononuclear phagocyte system. Staged rabbit embryos, from 14 to 28 days of age, were analysed and compared with findings from newborn and adult rabbits. No 13C2/23C6 immunoreactivity was seen in any of the tissues studied prior to day 17. 13C2/23C6-positive, mononuclear cells--presumptive osteoclast precursors--were first observed in the outer perichondrium of long-bones adjacent to the zone of hypertrophic cartilage in day 17 embryos. From day 17 onwards mono and multi-nucleate cells accumulated progressively in the perichondrium/periosteum, and by day 22 within the developing bone marrow cavity attached to bone spicules. No cells expressing the vitronectin receptor were seen at sites of embryonic or foetal haemopoiesis in yolk sac or foetal liver, that is, prior to the formation of the marrow cavity. Macrophages, defined by cross-reactivity with an antibody to human HLA-DR, first appeared in developing marrow spaces 11 days after the first osteoclast precursor appeared, suggesting that osteoclasts and definitive macrophages might develop from separate cell lineages, or that they diverge at an early stage of differentiation of haemopoietic stem cells.

Animals↗
PubMed1995

Expression of vitronectin receptor on human NK cells and its role in protein phosphorylation, cytokine production, and cell proliferation.

In this paper, we provide evidence that the vitronectin receptor (VNR) alpha v beta 3 is expressed on human NK cells. The presence of this VNR on freshly purified NK cells was demonstrated by flow cytometry analysis, as well as biochemically, after 125I-labeled surface lactoperoxidase labeling and immunoprecipitation. mAbs LM142 and LM609 specific for alpha v and alpha v beta 3, respectively, precipitated a heterodimer of alpha- and beta-chains with approximate molecular masses of 155 and 110 kDa under nonreducing conditions. Under reducing conditions, there was an apparent decrease in the molecular mass of the alpha-chain, which is likely to result from the release of a protein of 20 to 30 kDa linked by internal disulfide bond to the alpha v-chain. Integrin alpha v beta 3 expressed on NK cells became functional, i.e., was able to bind its ligand, vitronectin (VN), only after cellular activation or when costimulation with an additional signal was provided. Thus, NK cells adhered to plastic-immobilized VN only after IL-2 activation, and RGD-containing synthetic peptides or mAbs specific for alpha v beta 3 complex inhibited this binding. To assess the role of the VNR in signal transduction, anti-beta 3 mAb was used to cluster the VNR on NK cells and, thereby, mimic the process that occurs during formation of adhesive contacts. Cross-linking of VNR on fresh NK cells stimulated phosphorylation on tyrosine residues of several intracellular proteins. The major increase in tyrosine phosphorylation was observed in proteins of approximate molecular masses of 75 and 120 kDa. Therefore, signal transduction by the VNR on NK cells induced activation of intracellular protein kinases. Ligand engagement of the VNR on NK cells also costimulated cytokine production and proliferation of NK cells. Binding of NK cells to plastic-immobilized VN served as a costimulus with either anti-Fc gamma RIII or IL-2 to produce IFN-gamma, TNF-alpha, and cell proliferation. Our findings suggest that occupancy and subsequent clustering of VNRs play a role in the activation and function of human NK cells.

Amino Acid Sequence↗
PubMedDate not supplied

Quantitation and distribution of vitronectin in synovial fluid and tissue of patients with rheumatic disease.

OBJECTIVE: Our study was undertaken to determine the quantity and pattern of distribution of vitronectin (Vn) in the synovial fluid and tissue of patients with rheumatic disease. METHODS: We quantitated synovial fluid Vn levels in 37 patients (17 with rheumatoid arthritis (RA), 12 with crystal induced arthritis (CIA), and 8 with osteoarthritis (OA)) using a competitive-binding ELISA: Immunofluorescence studies were performed on synovial pannus tissue specimens from 3 RA patients. SDS-PAGE analysis of the synovial fluids was performed to demonstrate the molecular forms of Vn present in inflammatory and noninflammatory synovial fluids. Albumin levels of synovial fluids were determined using an automated chemistry analyzer. RESULTS: Immunoreactive Vn was detected in 36 of 37 synovial fluid specimens examined, over a wide range of dilutions. Concentrations of Vn in inflammatory synovial fluid were significantly elevated compared to non-inflammatory synovial fluid and normal human plasma (NHP). Immunofluorescence studies revealed immunoreactive Vn most heavily concentrated in the lining layers of RA pannus tissue. Similar to NHP, molecular forms of Vn were heterogeneous in the synovial fluid; however, the inflammatory milieu appears to predispose Vn to cleavage at its protease-sensitive site. Overall there was a positive correlation of synovial fluid Vn to albumin. CIA and OA revealed a very strong relationship, whereas RA synovial fluid Vn levels correlated poorly to the levels of albumin. CONCLUSION: Vitronectin is present in synovial fluid. Levels are significantly enhanced in the inflamed joint and in the RA synovial lining, where it may influence cell adhesion and modulate tissue repair.

Arthritis, Rheumatoid↗
PubMed1997

The suicide substrate reaction between plasminogen activator inhibitor 1 and thrombin is regulated by the cofactors vitronectin and heparin.

The interaction of thrombin with plasminogen activator inhibitor 1 (PAI-1) is shown to result in the simultaneous formation of both cleaved PAI-1 and a sodium dodecyl sulfate-stable thrombin-PAI-1 complex. The kinetics of this reaction can be described by a "suicide substrate" mechanism that includes a branched reaction pathway, which terminates in either the stable inhibitor-enzyme complex or the cleaved inhibitor plus free enzyme. Because of the branched pathway, approximately three moles of PAI-1 are needed to completely inhibit one mole of thrombin. Heparin and vitronectin enhance the rate of inhibition from 9.8 x 10(2) L mol(-1) s(-1) to 6.2 x 10(4) L mol(-1) s(-1) and 2.1 x 10(5) L mol(-1) s(-1), respectively, under optimal conditions. In addition to enhancing the rate of inhibition, both cofactors increase the apparent stoichiometry of the PAI-1-thrombin interaction, with cofactor concentration dependencies similar to the inhibition reaction. Thus, at 37 degrees C approximately six cleavage reactions occur per inhibition reaction. Therefore, thrombin will efficiently inactivate PAI-1 in the presence of either vitronectin or heparin, unless a sufficient excess of the inhibitor is present. These results show that physiological cofactors are able to switch a protease-serpin inhibition reaction to a substrate reaction, depending on the local concentrations of each of the components.

Animals↗
PubMed2003

Early vitronectin receptor downregulation in a melanoma cell line during all-trans retinoic acid-induced apoptosis.

BACKGROUND: Recent evidence assigns the vitronectin receptors (VnRs) an important role in regulating tumour cell invasion and dissemination. In vivo and in vitro studies document that all trans-retinoid acids (ATRAs) inhibit growth-inducing apoptosis in melanomas. OBJECTIVES: We have analysed the effects of ATRA treatment on melanoma cell adhesion and motility. METHODS: Human M14 melanoma cells were treated with 10 micromol L-1 ATRA for different times and stained with rhodamine-phalloidin to analyse the effect of treatment on cytoskeleton organization. Cell adhesion and cell migration assays were performed to analyse the role of VnRs in the ATRA-induced early stages of apoptosis. VnR expression was evaluated by Western blot, immunoprecipitation and immunocytochemistry assays. RESULTS: First, using an annexin V assay, we found that apoptosis was triggered by 48 h with 10 micromol L-1 ATRA exposure. At this time point, decrease in the F-actin polymerization as well as inhibition of cell adhesive ability to vitronectin (Vn) was exerted by ATRA treatment. In the presence of serum, exposure to 10 micromol L-1 ATRA for 48 h produced a dramatic inhibition of the cell adhesion ability that was comparable with that exerted by untreated cells preincubated with anti-alpha(v)beta(3) or anti-alpha(v)beta(5) VnR monoclonal antibodies. Functionally, the treatment of melanoma cells with 10 micromol L-1 ATRA for 48 h causes an inhibition of directional cell migration towards Vn-coated filters. Therefore, we analysed the effect of ATRA on the VnR expression. Both alpha(v)beta(3) and alpha(v)beta(5) VnR levels were reduced upon exposure to 10 micromol L-1 ATRA for 48 h as shown by Western blot, immunoprecipitation and immunocytochemistry assays. CONCLUSIONS: Altogether, our data indicate that treatment of M14 melanoma cells with ATRA downregulates VnR expression and that this reduction is closely correlated with the ATRA-dependent inhibition of actin-fibre organization, cell adhesion and migration. Although the mechanism by which ATRA regulates the expression of VnR in M14 melanoma cells needs further elucidation, this system may represent a model for understanding the molecular basis of ATRA therapy in melanoma.

Antineoplastic Agents↗
PubMed2006

Coordinate regulation of fibronectin matrix assembly by the plasminogen activator system and vitronectin in human osteosarcoma cells.

BACKGROUND: Plasminogen activators are known to play a key role in the remodeling of bone matrix which occurs during tumor progression, bone metastasis and bone growth. Dysfunctional remodeling of bone matrix gives rise to the osteoblastic and osteolytic lesions seen in association with metastatic cancers. The molecular mechanisms responsible for the development of these lesions are not well understood. Studies were undertaken to address the role of the plasminogen activator system in the regulation of fibronectin matrix assembly in the osteoblast-like cell line, MG-63. RESULTS: Treatment of MG-63 cells with P25, a peptide ligand for uPAR, resulted in an increase in assembly of fibronectin matrix which was associated with an increase in the number of activated beta1 integrins on the cell surface. Overexpression of uPAR in MG-63 cells increased the effect of P25 on fibronectin matrix assembly and beta1 integrin activation. P25 had no effect on uPAR null fibroblasts, confirming a role for uPAR in this process. The addition of plasminogen activator inhibitor Type I (PAI-1) to cells increased the P25-induced fibronectin polymerization, as well as the number of activated integrins. This positive regulation of PAI-1 on fibronectin assembly was independent of PAI-1's anti-proteinase activity, but acted through PAI-1 binding to the somatomedin B domain of vitronectin. CONCLUSION: These results indicate that vitronectin modulates fibronectin matrix assembly in osteosarcoma cells through a novel mechanism involving cross-talk through the plasminogen activator system.

Journal Article↗
PubMed1997

Melanoma cell migration on vitronectin: regulation by components of the plasminogen activation system.

Tumor cell migration and invasion require complex interactions between tumor cells and the surrounding extracellular matrix. These interactions are modified by cell adhesion receptors, as well as by proteolytic enzymes and their receptors. Here, we study the influence of the protease urokinasetype plasminogen activator (uPA) and its receptor (uPAR) on melanoma cell adhesion to, and migration on, the extracellular matrix protein vitronectin (VN). Cell adhesion to VN, but not to type I collagen, is significantly enhanced in the presence of either uPA or its amino-terminal fragment (ATF). Soluble uPAR can inhibit this effect, indicating that uPA/uPAR on melanoma cells can function as a VN receptor. In the absence of bivalent cations, uPA/uPAR can promote cell attachment on VN, but not cell spreading, suggesting that the glycosylphosphatidylinositol (GPI)-anchored uPAR alone is unable to organize the cytoskeleton. Chemotactic melanoma cell migration on a uniform VN matrix is inhibited by uPA and ATF, implying that cell motility decreases when uPA/uPAR acts as a VN receptor. In contrast, plasminogen activator inhibitor I (PAI-I) can stimulate melanoma cell migration on VN, presumably by inhibiting uPA/uPAR-mediated cell adhesion to VN and thereby releasing the inhibition of cell migration induced by uPA. Together, our data implicate components of the plasminogen activation system in the direct regulation of cell adhesion and migration, thereby modulating the behavior of malignant tumor cells.

Cell Movement↗
PubMed1994

Tetrafibricin has a high selectivity for GPIIb/IIIa: comparison of the effects of tetrafibricin and RGDS on GPIIb/IIIa and the vitronectin receptor.

The specificity of tetrafibricin was examined by comparing its activities on GPIIb/IIIa and on the vitronectin receptor (alpha v beta 3) with those of Arg-Gly-Asp-Ser (RGDS) on the same receptors. Tetrafibricin, which inhibited fibrinogen-GPIIb/IIIa binding 10 times more potently than RGDS, was three orders of magnitude less potent compared to RGDS on the inhibition of fibrinogen binding to alpha v beta 3. Furthermore, tetrafibricin potently inhibited platelet adhesion to both fibrinogen and von Willebrand factor. Whereas, there was no significant inhibition observed in the GPIIb/IIIa-independent cellular adhesions. These results suggest that tetrafibricin is highly selective for GPIIb/IIIa.

Amino Acid Sequence↗
PubMed1995

Constitutive alpha V beta 3 integrin-mediated adhesion of human lymphoid B cells to vitronectin substrate.

Adherence to cells and matrices participates in lymphocyte migration and tissue localization and contributes to the regulation of growth and differentiation of the lymphoid cells. The adherence is mainly mediated by three families of cell-surface proteins: integrins, immunoglobulin (Ig)-related molecules, and selectins. Integrins recognize Ig-related molecules such as ICAMs as well as fibronectin (FN), vitronectin (VN), and other matrix proteins. In this study, the in vitro adhesive properties of two Epstein-Barr virus-carrying B lymphoblastoid cell lines, IB-4 and NAD-20, were compared. IB-4 cells grow as a monolayer in contrast to NAD-20 cells, which grow as cell clusters. IB-4 cells were found to adhere to the tissue culture vessel through a component of the fetal bovine serum. By using blocking monoclonal antibodies to cell-surface molecules and serum proteins, IB-4 cells were found to use alpha V beta 3 integrin (CD51/CD61) and serum VN as the adhesive molecules. alpha V beta 3 integrin also mediated adhesion of IB-4 cells to human serum VN and to purified VN and FN. This constitutive adherence was not enhanced by phorbol ester treatment and was inhibited by RGD-containing peptides, in contrast to the homotypic adhesion of NAD-20 cells, which was mediated by beta 2 integrin CD11a/CD18 and its ligand ICAM-1 (CD54). Since VN is a component of both lymphoid tissue matrix and plasma, adhesion to this protein may affect functions and activities of B lymphocytes.

Amino Acid Sequence↗
PubMed2004

Role of alphavbeta5 integrins and vitronectin in Pseudomonas aeruginosa PAK interaction with A549 respiratory cells.

Bacterial adherence to mammalian cells and their internalization are thought to participate in Pseudomonas aeruginosa pathogenicity. In this study, we explored the role of alpha5beta1 and alphavbeta5 integrins and their natural ligands, fibronectin (Fn) and vitronectin (Vn), in P. aeruginosa interaction with epithelial cells by using the PAK reference bacterial strain, A549 respiratory, and SKOV-3 human ovarian cell lines. The host cell cytoskeleton and cellular tyrosine kinases seem to be solicited during the PAK-respiratory cell interaction: cytochalasin D and genistein decreased the bacterial adherence and internalization. Blocking antibodies to alphavbeta5 integrins were the only antibodies tested to have inhibitory activity against PAK adherence to A549 cells. PAK internalization by A549 and SKOV-3 cells was markedly decreased in the presence of blocking antibodies to Vn and alphavbeta5 integrins. Addition of Vn in excess restored PAK invasion of both A549 and SKOV-3 cells in the presence of anti-Vn antibodies. Immunofluorescence experiments revealed that, in the presence of bacteria, the Vn fibrillar network disappeared, and alphavbeta5 staining was concentrated in sites where adherent bacteria were present. Taken together, these findings suggest that alphavbeta5 integrins, and their natural ligand Vn, are involved in PAK entry into human epithelial cells.

Antibodies, Blocking↗
PubMed1995

Fibronectin, laminin, vitronectin and their receptors at newly-formed capillaries in proliferative diabetic retinopathy.

Proliferative diabetic retinopathy (PDR) is characterized by intraocular formation of fibroglial vascularized tissue by active vasoproliferative mechanisms. Using immunocytochemistry, we have studied changes in the distribution pattern of fibronectin (FN), laminin (LN), vitronectin (VN) and their receptors in the newly-formed capillaries of PDR. In intraocular vascularized tissue of PDR patients, FN was present on both luminal and basal surfaces of endothelial cells, and was diffusely distributed in the interpericyte space. LN was also associated with the interpericyte space. VN was occasionally detected on the luminal capillary side, but was frequent in the basal aspect of the endothelium in the interpericyte space, where it was colocalized with FN. Beta-1 subunit complex receptors were detected on the luminal side, while alpha v beta 3 integrin was identified on both sides, more so in the luminal than in the basal endothelial domain. By slot-blotting techniques and densitometric analysis, increased concentrations of intravitreous FN and VN were found in PDR in comparison with normal samples. These results suggest that FN, VN and LN have a key role in the structural arrangement of newly formed capillaries in PDR, and that receptor expression could be involved in events of endothelial cell adhesion and proliferation.

Adult↗
PubMedDate not supplied

Quantification of cell adhesion force with AFM: distribution of vitronectin receptors on a living MC3T3-E1 cell.

Distribution of vitronectin (VN) receptors on a living murine osteoblastic cell was successfully measured by atomic force microscopy (AFM). First, the distribution of the integrin beta(5) subunit which constitutes a part of the VN receptor on the cell was confirmed by conventional immunohistochemistry after fixing the cell. To visualize the distribution of the receptor on a living cell by an independent and potentially a more quantitative method, the AFM was used with a microbead attached to the cantilever tip to increase the area of contact and VN was immobilized on the microbead. Force measurements were then performed over a large area of a living murine osteoblastic cell using the microbead covered with VN.

Animals↗
PubMed2005

Plasminogen activator inhibitor type 1 promotes fibrosarcoma cell migration by modifying cellular attachment to vitronectin via alpha(v)beta(5) integrin.

Both urokinase plasminogen activator (u-PA) and plasminogen activator inhibitor type 1 (PAI-1) are associated with a poor prognosis in cancer patients. We demonstrate that PAI-1 inhibits human fibrosarcoma cell (HT-1080) adhesion to vitronectin (Vn) via alpha (v)beta (5) integrin, and stimulates cell migration from Vn toward collagen type IV (Col). The cells attached more strongly to Vn and Col than to fibronectin (Fn), whereas PAI-1 interfered with cell attachment to Vn only. An integrin antagonist, RGD peptide, and anti-alpha (v)beta (5) integrin antibodies, which similarly inhibited cell attachment to Vn, also stimulated cell migration from Vn toward Col. u-PA did not modify cell attachment directly, but reversed the PAI-1-mediated inhibitory effect on cell adhesion to Vn, and its stimulatory effect on cell migration from Vn toward Col. Thus HT-1080 cell migration appears to be modified by u-PA and PAI-1, altering cell adhesion to Vn via alpha (v)beta (5) integrin. This may be related to their tumor-promoting effect.

Cell Adhesion↗
PubMed1997

The cell adhesion domain in plasma vitronectin is cryptic.

Vitronectin (Vn) is a major adhesive glycoprotein in blood. However, many of the functions of Vn are regulated by its conformational state and degree of multimerization. Here, the ability of native and denatured Vn to bind to integrin adhesion receptors was compared. Three lines of evidence suggest that the native, plasma form of Vn is not an adhesive glycoprotein. (i) Antibodies that bind in close proximity to the cell adhesion domain of Vn fail to bind to native Vn present in unfractionated plasma. (ii) Denatured Vn binds to both glycoprotein IIb/IIIa and alphavbeta3 in a dose-dependent manner. In contrast, native Vn is unable to bind either integrin. (iii) Thermal denaturation of native Vn, or its complexation with type 1 plasminogen activator inhibitor, exposed the cell adhesion domain of Vn. Thus, while plasma Vn is unable to bind integrins and is not an adhesive glycoprotein, the conformationally altered from of the protein binds avidly to both alphavbeta3 and glycoprotein IIb/IIIa. The data presented here indicate that such conformational changes in Vn are likely to occur in areas of tissue injury and thrombosis.

Antibodies, Monoclonal↗