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PubMedDate not supplied

Human endothelial cells grow poorly on vitronectin: role of PAI-1.

The cell adhesive protein vitronectin is a common component of interstitial extracellular matrix and circulates in plasma. It competes effectively with other plasma proteins to adsorb to certain biomaterial surfaces, and is likely to represent an important cell adhesion mediator on the luminal surface of vascular grafts. It is also found associated with certain vascular pathologies. We have shown previously that human endothelial cells grow poorly on a vitronectin surface compared with other extracellular matrix molecules. In this paper we show that endothelial cells seeded on vitronectin and fibronectin produced substantially different profiles of extracellular matrix molecules. The most outstanding difference was in the amount of matrix-localised plasminogen activator-inhibitor-1 which was high on vitronectin and negligible on fibronectin. This was correlated with a small but significant inhibition of cell adhesion to vitronectin compared with fibronectin, and very significant interference with dissociation of cell: extracellular matrix contacts, resulting either from direct inhibition of the proteolytic activity of urokinase, or from interference with urokinase-receptor signaling and consequent focal adhesion turnover. Such interference would inhibit cell proliferation by disabling the cells from loosening their matrix contacts in order to proceed through mitosis. This would seriously compromise endothelial recovery in cases of damage to the vascular wall and placement of stents or grafts, where the presence of surface-adsorbed vitronectin is likely to modulate the tissue response.

Cell Adhesion↗
PubMed2001

Plasminogen activator inhibitor-1 regulates cell adhesion by binding to the somatomedin B domain of vitronectin.

Plasminogen activator inhibitor-1 (PAI-1) binds to the somatomedin B (SMB) domain of vitronectin. It inhibits the adhesion of U937 cells to vitronectin by competing with the urokinase receptor (uPAR; CD87) on these cells for binding to the same domain. Although the inhibitor also blocks integrin-mediated cell adhesion, the molecular basis of this effect is unclear. In this study, the effect of the inhibitor on the adhesion of a variety of cells (e.g., U937, MCF7, HT-1080, and HeLa) to vitronectin was assessed, and the importance of the SMB domain in these interactions was determined. Although PAI-1 blocked the adhesion of all of these cells to vitronectin-coated wells, it did not block adhesion to a variant of vitronectin which lacked the SMB domain. Interestingly, HT-1080 and U937 cells attached avidly to microtiter wells coated with purified recombinant SMB (which does not contain the RGD sequence), and this adhesion was again blocked by the inhibitor. These results affirm that PAI-1 can inhibit both uPAR- and integrin-mediated cell adhesion, and demonstrate that the SMB domain of vitronectin is required for these effects. They also show that multiple cell types can employ uPAR as an adhesion receptor. The use of purified recombinant SMB should help to further define this novel adhesive pathway, and to delineate its relationship with integrin-mediated adhesive events.

Antigens, CD↗
PubMed1991

Vitronectin-induced haptotaxis of vascular smooth muscle cells in vitro.

Vitronectin, a multifunctional glycoprotein present in the plasma and interstitial tissues, has recently been found to be localized in atherosclerotic lesions. In this study we examined the effects of vitronectin on the migration of cultured bovine aortic smooth muscle cells using a modified Boyden chamber assay. The cells migrated to fluid-phase vitronectin in a concentration-dependent fashion. The cells also migrated to membrane filter surfaces precoated with vitronectin for a few minutes in the absence of additional vitronectin in the fluid phase, suggesting that this substance binds easily to the filters and stimulates cell migration by haptotaxis under the conditions described. These observations suggest that vitronectin deposited in the intima may be involved in the pathogenesis of atherosclerosis by recruiting smooth muscle cells from the media into the intima.

Animals↗
PubMed1992

Activation of the collagen-binding of endogenous serum vitronectin by heating, urea and glycosaminoglycans.

The present study describes that the collagen-binding activity of vitronectin in human serum increases by treatment with heparin, heating and urea. Vitronectin purified from human serum was bound to native collagen, whereas endogenous vitronectin in the serum was not. We have examined the conditions to change the collagen-binding activity of endogenous vitronectin. Endogenous vitronectin in human serum became considerably bound to collagen when the serum was boiled in 4-8 M urea for 5 min and mixed with heparin (0.5-5 micrograms/ml). Each treatment of heating, urea or heparin alone, and any combination of the two factors, inefficiently activated the binding. Dextran sulfate could substitute for heparin, but dermatan sulfate, keratan sulfate, chondroitin sulfate A and C, heparan sulfate and hyaluronan could not. Possible explanations for the activation of endogenous vitronectin are discussed.

Blood Proteins↗
PubMed1997

Plasma vitronectin concentrations in patients with chronic hepatitis C treated with interferon alpha.

Plasma vitronectin concentration was measured in 60 patients with chronic hepatitis C before and after interferon alpha treatment. The plasma pretreatment levels of vitronectin in the interferon non-responders was significantly lower than those in the interferon sustained and transient responders, but the levels were not different in the latter two groups. After interferon therapy, the plasma levels of vitronectin were significantly increased in all three groups, and they were correlated with the albumin levels. Absolute changes of plasma vitronectin before and after interferon treatment were significantly related to initial levels, but they were not related to those of albumin or alanine aminotransferase levels. The values of sensitivity and specificity for plasma vitronectin in the sustained responder and non-responder were 45% and 95% for each. These results suggest that chronic hepatitis C patients with low levels of plasma vitronectin may have a weak response in interferon therapy.

Alanine Transaminase↗
PubMedDate not supplied

Role of vitronectin receptor-type integrins and osteopontin in ischemia-induced retinal neovascularization.

PURPOSE: It has been reported that vitronectin receptor-type integrins mediate vascular cell proliferation and migration. In this study, we investigated the expression of vitronectin receptor-type integrins and osteopontin in ischemia-induced retinal neovascularization, and examined the role of osteopontin in angiogenesis as a ligand of vitronectin receptor-type integrins. METHODS: Retinal neovascularization was produced by exposing C57BL/6J mice to 75% oxygen from postnatal day (P) 7 to P12. Expression of vitronectin receptor-type integrins and osteopontin was assessed by Northern blot analysis, in situ hybridization, and immunofluorescence. The role of osteopontin in retinal angiogenesis was evaluated by tube formation assay using cultured bovine retinal microcapillary endothelial cells. RESULTS: In the murine model, integrin alpha(v) mRNA was increased from P14 with a 2.6-fold peak response observed on P19, when retinal neovascularization was remarkable. Indirect immunofluorescence for vitronectin receptor-type integrins revealed prominent expression of integrin alpha(v)beta3/beta5 in the neovascular endothelial cells. Osteopontin mRNA was increased from P14, with a 2.0-fold peak response observed on P19. In situ hybridization demonstrated localization of osteopontin mRNA in neovascular tufts. Vascular endothelial growth factor-induced tube formation (8.3 +/- 0.6 mm/field) was inhibited significantly by treatment with anti-osteopontin antibody (4.8 +/- 0.7 mm/field, P <.001). CONCLUSIONS: These data suggest that increased expression of both vitronectin receptor-type integrins and osteopontin in ischemic retina contribute to vascular endothelial cell proliferation and to retinal vascular formation by promoting interaction between endothelial cells and extracellular matrix, which leads to retinal neovascularization.

Animals↗
PubMed1999

Protein disulfide isomerase catalyzes the formation of disulfide-linked complexes of vitronectin with thrombin-antithrombin.

In this study, purified preparations of platelet protein disulfide isomerase (PDI), vitronectin, alpha-thrombin, and antithrombin (AT) were used to demonstrate that PDI catalyzes formation of vitronectin-thrombin-AT complexes. Complex formation requires reduced glutathione (GSH) and can be prevented by N-ethymaleimide, and the formed complex is dissociated by reducing agents such as mercaptoethanol. No vitronectin-thrombin complex formed in the absence of AT, indicating that the thrombin-AT complex is an obligate intermediate in the reaction. Under optimal conditions, the majority of the thrombin-AT is incorporated into the complex in 60 min. Thrombospondin-1, known to form disulfide-linked complexes with thrombin-AT [Milev, Y., and Essex, D. W. (1999) Arch. Biochem. Biophys. 361, 120-126], competes with vitronectin for thrombin-AT in the low-Ca(2+) environment that favors the active form of thrombospondin. The results presented here may also explain previous studies showing that vitronectin-thrombin-AT complexes form better in plasma (which contains PDI) than with purified proteins (where PDI was not used). We were able to purify a PDI from plasma that was immunologically identical to the platelet enzyme. We used the scrambled RNase assay to show that added purified PDI can function in a plasma environment. Complex formation in plasma was inhibited by inhibitors of PDI. PDI was released from the platelet surface in a soluble form at high pH (around the physiologic range), suggesting a source of the plasma PDI. In summary, these studies indicate that PDI functions to form disulfide-linked complexes of vitronectin with thrombin-AT.

Animals↗
PubMed1996

Characterization of the denaturation and renaturation of human plasma vitronectin. II. Investigation into the mechanism of formation of multimers.

Unfolding and refolding of plasma vitronectin appear irreversible under near physiological conditions, with rearrangements of disulfides and self-association to a multimeric form observed as prominent structural alterations which accompany denaturation. A mechanism for the folding reactions of vitronectin has been proposed (Zhuang, P., Blackburn, M. N., and Peterson, C. B.(1996) J. Biol. Chem. 270, 14323-14332) in which vitronectin acquires a partially folded intermediate structure which is highly prone to oligomerize into a multimeric form. Strongly oxidizing conditions adopted for refolding from urea were effective at preventing disulfide rearrangement which disrupts distal disulfides near the C terminus of the protein. Prohibiting disulfide rearrangement under these conditions, however, was not sufficient to achieve reversibility in folding. In contrast, variations in the ionic strength of the refolding medium affect the partitioning of species so that refolded monomers are obtained at high ionic strength, and self-association is precluded. The effects of ionic strength on the partially folded intermediate in the vitronectin folding pathway appear to favor intramolecular hydrophobic collapse to form a stable hydrophobic core for the monomer versus intermolecular hydrophobic interactions which stabilize multimeric vitronectin. Although both ionic and hydrophobic interactions presumably contribute to subunit interfaces within the multimer, the basic heparin-binding region near the C terminus of the protein does not provide binding interactions which are important for self-association of vitronectin.

Amino Acid Sequence↗
PubMed2006

Defining the native disulfide topology in the somatomedin B domain of human vitronectin.

The N-terminal 44 amino acid residues of the human plasma glycoprotein vitronectin, known as the somatomedin B (SMB) domain, mediates the interaction between vitronectin and plasminogen activator inhibitor 1 (PAI-1) in a variety of important biological processes. Despite the functional importance of the Cys-rich SMB domain, how its four disulfide bridges are arranged in the molecule remains highly controversial, as evidenced by three different disulfide connectivities reported by several laboratories. Using native chemical ligation and orthogonal protection of selected Cys residues, we chemically synthesized all three topological analogs of SMB with predefined disulfide connectivities corresponding to those previously published. In addition, we oxidatively folded a fully reduced SMB in aqueous solution, and prepared, by CNBr cleavage, the N-terminal segment of 51 amino acid residues of intact vitronectin purified from human blood. Proteolysis coupled with mass spectrometric analysis and functional characterization using a surface plasmon resonance based vitronectin-PAI-1-SMB competition assay allowed us to conclude that 1) only the Cys(5)-Cys(21), Cys(9)-Cys(39), Cys(19)-Cys(32), and Cys(25)-Cys(31) connectivity is present in native vitronectin; 2) only the native disulfide connectivity is functional; and 3) the native disulfide pairings can be readily formed during spontaneous (oxidative) folding of the SMB domain in vitro. Our results unequivocally define the native disulfide topology in the SMB domain of human vitronectin, providing biochemical as well as functional support to the structural findings on a recombinant SMB domain by Read and colleagues (Zhou, A., Huntington, J. A., Pannu, N. S., Carrell, R. W., and Read, R. J. (2003) Nat. Struct. Biol. 10, 541-544).

Cysteine↗
PubMed1995

PCR-amplified vitronectin mRNA localizes in situ to spermatocytes and round spermatids in the human testis.

Vitronectin is an adhesion protein present within the acrosomal cap region of human spermatozoa and is liberated during the acrosome reaction. The purpose of this study was to determine if vitronectin mRNA was synthesized in the male genital tract using the reverse transcriptase in-situ polymerase chain reaction (PCR) technique. Twelve genital tract tissues, which included six testes, one showing Sertoli cells only and one from a 3 year old boy, as well as sections from the prostate, seminal vesicles, and epididymis, were analysed for vitronectin transcripts. PCR-amplified vitronectin cDNA was detected in the seminiferous tubules of the four adult testes that showed normal spermatogenesis and localized to the spermatocytes and round spermatids. PCR-amplified vitronectin cDNA was not detected in the tissues of the prostate, epididymis, and seminal vesicles from the men whose testes did contain the message, nor in the testes with Sertoli cells only or that of the prepubertal boy. It is concluded that, in the male genital tract, vitronectin is transcribed exclusively in the germ cells at the spermatocyte and round spermatid stages. This demonstrates that the translated protein present in the spermatozoon is being produced in situ. Further study is needed to determine the role of this protein in the dynamics of sperm-oocyte interaction.

Adult↗
PubMed1994

Evidence that the heparin-binding consensus sequence of vitronectin is recognized by Staphylococcus aureus.

Binding of heparin-binding form of vitronectin to Staphylococcus aureus was inhibited completely by heparin or by the same form of vitronectin. The binding was inhibited only to about 50% by the non-heparin-binding form of vitronectin, indicating an apparent involvement of the heparin-binding properties in the interaction between vitronectin and S. aureus. This was supported by experiments in which a synthetic peptide (Ala347-Arg361, comprising heparin-binding consensus sequences) was found to partly inhibit bacterial adherence to immobilized vitronectin. A bacterial cell surface protein could bind to the quinquedecapeptide, but not to the highly charged peptides consisting entirely of arginine or lysine, immobilized on microtiter plates and the binding could be competitively inhibited by an excess of soluble peptide. Direct binding of radiolabeled peptide to bacterial cells was also demonstrated, which was rapid, saturable, and pH-dependent. Furtherly a bacterial surface protein having molecular mass of 60 kDa was isolated by affinity chromatography on a quinquedecapeptide-HiTrap-NHS column. Our data suggest that the heparin-binding properties of vitronectin play a role in bacterial recognition.

Amino Acid Sequence↗
PubMed1990

Fibrillin immunoreactive fibers constitute a unique network in the human dermis: immunohistochemical comparison of the distributions of fibrillin, vitronectin, amyloid P component, and orcein stainable structures in normal skin and elastosis.

Fibrillin, a 350-kD glycoprotein, was recently localized to elastin-associated 10 nm microfibrils. Here, the distribution of fibrillin immunoreactivity was determined in normal skin in individuals of different ages and in lesions of solar elastosis or anetoderma. It was compared with the distribution of orcein-stainable fibers and with the immunoreactivities of vitronectin and amyloid P component. These glycoproteins are known to occur in conjunction with the orcein-stainable elastic fibers in adults, but not in the young. Fibrillin immunoreactivity was associated with orcein-stainable fibers in normal skin of both adults and the young. In addition, the fibrillin immunoreactive fiber network comprised fine fibers that were unstainable by orcein, anti-vitronectin, or anti-amyloid P component. Such fine fibers were especially abundant close to the dermal-epidermal junction zone. Immunoreactivities of anti-vitronectin and anti-amyloid P component were not always associated with fibrillin immunoreactivity but were consistently found to co-localize with orcein-stainable fibers in adults. This suggests vitronectin and amyloid P component to be associated with the amorphous elastin rather than with the microfibrils, although alternative interpretations are possible. In elastotic lesions, fibrillin immunoreactivity was generally fainter than that obtained using anti-vitronectin or anti-amyloid P component. In contrast, an extensive network of dermal fibers stained by anti-fibrillin, but not by anti-amyloid P component, anti-vitronectin, or orcein, was seen in an anetoderma lesion. In conclusion, fibrillin immunoreactivity is associated with a unique dermal network, which ultrastructurally is composed of microfibrils. These fibers are proposed to have an important structural and functional role in anchoring the dermal elastic fibers in the extracellular matrix and to the lamina densa.

Connective Tissue Diseases↗
PubMed1993

Vitronectin-mediated inhibition of complement: evidence for different binding sites for C5b-7 and C9.

In the activated complement system, vitronectin (complement S-protein) occupies the metastable membrane binding site of the nascent precursor complex C5b-7, so that the newly formed SC5b-7 is unable to insert into cell membranes. Some evidence also indicates that vitronectin limits on-going membrane-associated pore formation by inhibiting C9 polymerization. It has been assumed that these two stages of terminal complement complex (TCC) inhibition take place through charge interactions between the heparin-binding region of vitronectin and homologous cysteine-rich sequences of the late complement proteins C6, C7, C8 and C9. We examined SC5b-7 formation and inhibition of C9 binding in the TCC using separate haemolytic assays. The mode of action of vitronectin in these assays was compared with two 15mer peptides which span residues 348-379 of the heparin-binding region, and a heparin-affinity polypeptide, protamine sulphate. The results showed that vitronectin acts predominantly through SC5b-7 production with a lesser effect on the inhibition of C9 lytic pore formation. In contrast, protamine sulphate did not prevent C5b-7 membrane attachment, but was a potent inhibitor of C9-mediated lysis. The peptides did not inhibit C5b-7 membrane insertion and only one affected C9 binding. These data suggest that the two stages of TCC inhibition involve separate binding sites on the vitronectin molecule. The site for association with nascent C5b-7 is unknown, whereas inhibition of C9 binding and pore formation takes place through the heparin-binding region.

Amino Acid Sequence↗
PubMed1995

Complement inhibition by human vitronectin involves non-heparin binding domains.

Vitronectin (complement S-protein), a multifunctional glycoprotein, inhibits complement-mediated cytolysis at two identified stages of terminal complement complex (TCC) formation: blocking of C5b-7 membrane binding, and prevention of C9 polymerization. However, the functional domain(s) of vitronectin involved in these reactions remains incompletely defined. In order to identify the complement inhibition site, a 12-kD heparin binding fragment and two other internal fragments (53 kD and 43 kD) of vitronectin were isolated after cyanogen bromide (CNBr) treatment of the native molecule. Potent inhibition of guinea pig erythrocyte (GPE) reactive lysis was demonstrated with native vitronectin, total CNBr digest and the 53-kD and 43-kD fragments, but only very poorly by the heparin binding 12-kD peptide. Similarly, the 43-kD fragment blocked the binding of C5b-7 to immobilized vitronectin, whereas the 12-kD fragment had no effect. These data localize the C5b-7 binding site to a 43-kD internal region. Further characterization of the fragments was carried out in an assay which detected C9 polymerization in the presence of C5b-8. Polymerized material was separated by PAGE, detected by autoradiography and quantified after excision from the gels. Results showed that polymerization did not occur in the presence of the 53-kD and 43-kD fragments. However, the 12-kD heparin binding fragment had no effect. It is proposed that prevention of C5b-8-induced C9 polymerization resides at a site in an internal region of the vitronectin molecule.

Amino Acid Sequence↗
PubMed2001

Integrin binding to fibronectin and vitronectin maintains the barrier function of isolated porcine coronary venules.

Integrin-mediated endothelial cell-extracellular matrix adhesion plays a critical role in maintaining the structural integrity of microvascular walls. The aim of this study was to evaluate the impact of specific integrin extracellular domain binding to matrix fibronectin and vitronectin on the barrier function of intact microvascular endothelium. The apparent permeability coefficient of albumin was measured in isolated and perfused porcine coronary venules using a fluorescence ratioing technique with the aid of fluorescence microscopy. Inhibition of integrin binding to either fibronectin with GRGDdSP peptide or vitronectin with GPenGRGDSPCA peptide dose-dependently increased venular permeability by 2- to 3-fold. The effects were sustained for more than 60 min and were reversible upon clearance of the peptides. In contrast, the inactive control peptide GRADSP did not significantly affect venular permeability. Pretreatment of the venules with purified human fibronectin and vitronectin, respectively, prevented the hyperpermeability response to GRGDdSP and GPenGRGDSPCA. GRGDSP, a peptide that inhibits integrin binding to both fibronectin and vitronectin, produced an even higher permeability (4.5-fold) in venules than GRGDdSP or GPenGRGDSPCA alone, and the effect was blunted in vessels preincubated with both fibronectin and vitronectin. The results indicate the importance of integrin-matrix interaction in the physiological regulation of microvascular permeability. It is likely that both fibronectin and vitronectin binding to integrins contribute to the maintenance of endothelial barrier function in venules.

Animals↗
PubMed1997

Vitronectin mediates internalization of Neisseria gonorrhoeae by Chinese hamster ovary cells.

Gonococci producing a distinct opacity protein (OpaA in strain MS11) adhere to and are efficiently internalized by cultured epithelial cells such as the Chang conjunctiva cell line. Both adherence and uptake require interactions between OpaA and heparan sulfate proteoglycans on the mammalian cell surface. Chinese hamster ovary (CHO) cells also support adherence of gonococci through interactions of OpaA with cell surface heparan sulfate proteoglycans. However, despite this similarity in the requirements for adherence, CHO cells are not capable of internalizing gonococci. In this report, we characterized this apparent deficiency and identified a factor in fetal calf serum (FCS) which is capable of mediating uptake of gonococci by CHO cells. In the absence of FCS, OpaA+ gonococci adhered to but were not internalized by CHO cells, whereas in the presence of up to 15% FCS, the bacteria were efficiently internalized by the cells. Preincubation of bacteria, but not cells, with FCS also stimulated internalization, suggesting that a factor present in FCS was binding to the surface of gonococci and subsequently stimulating entry. Using a combination of chromatographic purification procedures, we identified the adhesive glycoprotein vitronectin as the serum factor which mediates the internalization of gonococci by CHO cells. Vitronectin-depleted serum did not support gonococcal entry, and this deficiency was restored by the addition of purified vitronectin. Further experiments using a set of gonococcal recombinants, each expressing a single member of the family of Opa outer membrane proteins, demonstrated that vitronectin bound to the surface of OpaA-producing gonococci only and that the vitronectin-mediated uptake by the CHO cells was limited to this bacterial phenotype. To our knowledge, our data are the first example that vitronectin can serve as a molecule that drives bacterial entry into epithelial cells.

Animals↗
PubMed2006

Binding of vitronectin by the Moraxella catarrhalis UspA2 protein interferes with late stages of the complement cascade.

Many Moraxella catarrhalis strains are resistant to the bactericidal activity of normal human serum (NHS). The UspA2 protein of the serum-resistant strain O35E has previously been shown to be directly involved in conferring serum resistance on this strain. Testing of 11 additional serum-resistant M. catarrhalis wild-type isolates and their uspA1 and uspA2 mutants showed that the uspA1 mutants of all 11 strains were consistently serum resistant and that the uspA2 mutants of these same 11 strains were always serum sensitive. Analysis of complement deposition on four different serum-resistant M. catarrhalis strains and their serum-sensitive uspA2 mutants showed that, for three of these four strain sets, the wild-type and mutant strains bound similar amounts of early complement components. In contrast, there was a significant reduction in the amount of the polymerized C9 on the wild-type strains relative to that on the uspA2 mutants. These same three wild-type strains bound more vitronectin than did their uspA2 mutants. UspA2 proteins from these three strains, when expressed in Haemophilus influenzae, bound vitronectin and conferred serum resistance on this organism. Furthermore, vitronectin-depleted NHS exhibited bactericidal activity against these same three serum-resistant wild-type strains; addition of purified vitronectin to this serum restored serum resistance. In contrast, binding of the complement regulator C4b-binding protein by the M. catarrhalis strains used in this study was found to be highly variable and did not appear to correlate with the serum-resistant phenotype. These results indicate that binding of vitronectin by UspA2 is involved in the serum resistance of M. catarrhalis; this represents the first example of vitronectin-mediated serum resistance on a microbe.

Bacterial Outer Membrane Proteins↗
PubMedDate not supplied

Increased vitronectin and endothelin-1 in the breath condensate of patients with fibrosing lung disease.

BACKGROUND: Non-specific interstitial pneumonia (NSIP) and fibrosing alveolitis associated with systemic sclerosis (FASSc) are diseases of unknown aetiology that are characterised by the accumulation of mononuclear cells, followed by the progressive deposition of collagen within the interstitium and subsequent destruction of lung airspace. Better understanding of mediators involved in fibrosis may be useful for early diagnosis and in clinical monitoring of disease progression. OBJECTIVE: The aim of this study was to investigate the presence of two profibrotic markers, the vitronectin and the endothelin-1 (ET-1) in the airways of NSIP and FASSc patients. METHODS: Ten NSIP (6 males, age 57 +/- 2 years) and 15 FASSc (8 males, age 55 +/- 4 years) patients were recruited along with 10 normal subjects (4 male, age 52 +/- 2 years). Vitronectin and ET-1 concentrations were measured in their breath condensate, using a specific enzyme immunoassay. RESULTS: Higher levels of vitronectin and ET-1 were observed in NSIP and FASSc patients [median 92.8 (91.7-93.9) microg/ml; median 8.3 (7.9-9.3) pg/ml] than in control subjects [median 80.3 (89.3-91.4) microg/ml; p < 0.01; median 5.3 (4.9-5.9) pg/ml, p < 0.0001]. We also found increased concentrations of vitronectin in patients with clinical deterioration compared to those remaining stable and in ex-smokers compared to non-smokers and, increased vitronectin and ET-1 in patients treated with steroids compared to untreated patients. CONCLUSION: These findings justify further studies of vitronectin and ET-1 levels in exhaled breath condensate, as a means of monitoring activity and predicting progression of pulmonary fibrosis.

Biomarkers↗