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PubMed2000

The Preterm Prediction Study: sequential cervical length and fetal fibronectin testing for the prediction of spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVES: This study was undertaken to further elucidate the pathogenesis of preterm birth by means of traditional risk factors and new markers for preterm birth derived from the Preterm Prediction Study. STUDY DESIGN: A total of 3076 women (2929 with singleton gestations and 147 with twin pregnancies) were categorized according to the presence of risk factors including black race, low body mass index, the presence of bacterial vaginosis, and previous preterm birth. At 24 and 28 weeks' gestation cervical length was measured and categorized as short (</=25 mm) or normal (>25 mm). Vaginal and cervical fetal fibronectin concentrations were measured at 24, 26, 28, and 30 weeks' gestation and results were categorized as positive (>/=50 ng/mL) or negative (<50 ng/mL). RESULTS: At 24 to 26 weeks' gestation women with each of the risk factors were more likely to have positive fibronectin test results or to have a short cervix. Among women with negative fetal fibronectin results at 24 to 26 weeks' gestation those with a short cervix were more likely to have positive fetal fibronectin results at 28 to 30 weeks' gestation, and among those with normal cervical length those women who had positive fetal fibronectin results were more likely to have a short cervix at later evaluation. Most women who had positive fetal fibronectin results at 24 to 26 weeks' gestation had negative results at 28 to 30 weeks' gestation, whereas most but not all women who had a short cervix at 24 to 26 weeks' gestation still had a short cervix at 28 to 30 weeks' gestation. In each period women with both a positive fetal fibronectin result and a short cervix were at substantially increased risk of spontaneous preterm birth; women with either marker alone had intermediate and approximately equal risks of spontaneous preterm birth, and women without either marker had a low risk of spontaneous preterm birth. CONCLUSION: Regardless of other risk factors, a short cervix predicts a subsequent positive fetal fibronectin result, and a positive fetal fibronectin result predicts subsequent cervical shortening. These data do not support a single sequence of events leading to spontaneous preterm birth.

Biomarkers↗
PubMed1996

Expression of oncofetal fibronectin in porcine conceptuses and uterus throughout gestation.

Oncofetal fibronectin is reportedly expressed specifically by trophoblast tissue and some tumours and speculated to mediate placental attachment. In the present study, a monoclonal antibody (FDC-6) to human oncofetal fibronectin was used to characterize temporal and spatial changes in the expression of oncofetal fibronectin at the fetal-maternal interface of pigs. Conceptus and uterine tissues were collected from gilts throughout normal pregnancy and processed for immunohistochemical characterization. Results indicated that oncofetal fibronectin was constitutively expressed by both porcine conceptus and uterus throughout gestation. The most abundant staining for oncofetal fibronectin was found in the allantochorion and detectable levels of oncofetal fibronectin were also detected in luminal and glandular epithelial cells in the uterus. During the second-half of pregnancy, oncofetal fibronectin was also detected in fibroblast-like cells in the uterine stroma, but not in the stroma of the allantochorion. Owing to the non-invasive nature of the porcine placenta, the abundant expression of oncofetal fibronectin by the trophoblast and uterus may influence attachment between chorion and endometrium during pregnancy. Since attachment is the first step in implantation and placentation in all mammalian species, the pig may represent an excellent animal model to study interactions between trophoblast and endometrium mediated by oncofetal fibronectin.

Animals↗
PubMed1982

Fibronectin binds to the C1q component of complement.

Fibronectin immobilized to plastic tubes binds soluble C1q with a Kd of 82 +/- 2.6 nM. The binding of fibronectin to C1q is relatively insensitive to pH but is sensitive to ionic conditions. C1q covalently bound to Sepharose selectively binds cellular fibronectin produced by a hamster fibroblast cell line. The globular head regions of C1q have no effect on the binding of C1q to fibronectin but the collagenous tails of C1q interfere competitively with a Ki of 59 nM. We conclude that fibronectin binds C1q via its collagen-like tail region and thus the process resembles the binding of fibronectin to gelatin. This is further emphasized by our observation that gelatin binds to fibronectin immobilized on plastic tubes with a Kd of 131 nM. Because fibronectin stimulates endocytosis in several systems and promotes the clearance of particulate material from the circulation, these results suggest the possibility that fibronectin could function in the clearance of C1q-coated material such as immune complexes or cellular debris.

Animals↗
PubMed1985

Mammalian reticulocytes lose adhesion to fibronectin during maturation to erythrocytes.

We describe three situations in which a large fraction of circulating red blood cells attach tightly and specifically to fibronectin: (i) rabbits made anemic by repeated bleeding, (ii) patients with hemolytic anemia and functional asplenia and splenectomized normal humans, and (iii) splenectomized mice. Upon induction of anemia in rabbits, the proportion of circulating red blood cells capable of specifically attaching to fibronectin-coated plastic increased in parallel with the number of reticulocytes. Fibronectin-adherent red cells were barely detectable when the rabbit had recovered from the anemia. Attachment of reticulocytes to fibronectin was specific; cells did not attach to dishes coated with albumin, laminin, or collagen. None of these proteins promoted the attachment of normal erythrocytes. About 75% of the erythrocytes from splenectomized mice (but not control mice) also attached specifically to fibronectin 40 days after surgery. The effect of splenectomy was incomplete and transient; adherent cells were not detectable 8 weeks after splenectomy. As judged by labeling studies with [35S]methionine, newly emergent reticulocytes preferentially attached to fibronectin. We suggest that about half of the reticulocytes in erythropoietically unstressed mice lose their ability to attach to fibronectin, possibly due to loss of fibronectin-adhesive components, during passage through the spleen. The others lose their ability to interact with fibronectin before release, in the bone marrow, or in some extrasplenic site.

Anemia, Sickle Cell↗
PubMed1985

Incorporation of cellular and plasma fibronectins into smooth muscle cell extracellular matrix in vitro.

Fibronectins isolated from the conditioned medium produced by cultures of undifferentiated (monolayer) and differentiated (nodular) swine vascular smooth muscle cells are similar but not identical. In general, the nodular-cell fibronectin has a smaller molecular mass than monolayer-cell fibronectin and appears to lack the COOH-terminal interchain disulfide linkage. We studied the incorporation of cellular and plasma fibronectins into the cell layer. Smooth muscle cells bound 2.5 times more monolayer-cell fibronectin than nodular-cell fibronectin. Polypeptide fragments of human plasma fibronectin were used as a model system to investigate fibronectin incorporation into the cell layer. Only intact molecules were incorporated into the cell layer and subsequently organized into fibers. Polypeptide fragments of molecular mass 205 kDa and 185 kDa were not incorporated even though they retained the collagen-, cell-, and heparin-binding regions. Incorporation appears to require an activity associated with either the NH2-terminal or COOH-terminal domains. We propose that fibronectin activity is lost during differentiation of smooth muscle cells.

Animals↗
PubMed2005

Identification of a novel recognition sequence for fibronectin within the NH2-terminal beta-sandwich domain of tissue transglutaminase.

Tissue transglutaminase belongs to the multigene transglutaminase family of Ca2+-dependent protein cross-linking enzymes. Unlike other transglutaminases, it is involved in cell-matrix interactions and serves as an adhesion co-receptor for fibronectin. Previous work established that the fibronectin-binding motif(s) is located within the NH2-terminal proteolytic fragment of the protein consisting of residues 1-272. Here we identify a novel fibronectin recognition site within this sequence of tissue transglutaminase. Substitution of individual domains of tissue transglutaminase with those from homologous factor XIIIA showed that the major fibronectin-binding site is present within the first beta-sandwich domain of the protein. Experiments with deletion mutants of the first domain revealed that amino acids 81-140 of tissue transglutaminase are involved in fibronectin binding. Using synthetic peptides encompassing this region, we found that the peptide 88WTATVVDQQDCTLSLQLTT106 inhibited the interaction of tissue transglutaminase with fibronectin and decreased transglutaminase-dependent cell adhesion and spreading. In the three-dimensional structure of the first domain, amino acids 88-106 comprise an extended hairpin formed by antiparallel beta strands 5 and 6. Mutations of Asp94 and Asp97 within the beta5/beta6 hairpin to Ala significantly reduced the affinity of tissue transglutaminase for fibronectin, indicating that these residues are critical for fibronectin binding. Identification of the fibronectin-binding site on tissue transglutaminase will help to dissect the role of this protein in cell-matrix interactions.

3T3 Cells↗
PubMed2006

Identification of the heparin-binding determinants within fibronectin repeat III1: role in cell spreading and growth.

Fibronectins are high molecular mass glycoproteins that circulate as soluble molecules in the blood, and are also found in an insoluble, multimeric form in extracellular matrices throughout the body. Soluble fibronectins are polymerized into insoluble extracellular matrix (ECM) fibrils via a cell-dependent process. Recent studies indicate that the interaction of cells with the ECM form of fibronectin promotes actin organization and cell contractility, increases cell growth and migration, and enhances the tensile strength of artificial tissue constructs; ligation of integrins alone is insufficient to trigger these responses. Evidence suggests that the effect of ECM fibronectin on cell function is mediated in part by a matricryptic heparin-binding site within the first III1 repeat (FNIII1). In this study, we localized the heparin-binding activity of FNIII1 to a cluster of basic amino acids, Arg613, Trp614, Arg615, and Lys617. Site-directed mutagenesis of a recombinant fibronectin construct engineered to mimic the ECM form of fibronectin demonstrates that these residues are also critical for stimulating cell spreading and increasing cell proliferation. Cell proliferation has been tightly correlated with cell area. Using integrin- and heparin-binding fibronectin mutants, we found a positive correlation between cell spreading and growth when cells were submaximally spread on ECM protein-coated surfaces at the time of treatment. However, cells maximally spread on vitronectin or fibronectin still responded to the fibronectin matrix mimetic with an increase in growth, indicating that an absolute change in cell area is not required for the increase in cell proliferation induced by the matricryptic site of FNIII1.

Amino Acid Motifs↗
PubMed1987

Unilateral paraquat-induced lung fibrosis: evolution of changes in lung fibronectin and collagen after graded degrees of lung injury.

We describe a model of pulmonary fibrosis in which doses of paraquat ranging from 0.001 mg/kg to 1.0 mg/kg were instilled into the right lung of rats. Lung injury, as measured by right lung lavage albumin content and differential neutrophil count, ranged from undetectable to extremely severe, depending on the dose. Lung fibrosis, as assessed by collagen content and electron microscopy, showed similar dose-response effects. Mortality was minimal. Lavage fibronectin increased after high doses of paraquat, peaked at 2 d postinjury, decreased sharply after 3 d and was normal by 7 d. The temporal pattern was similar to that for albumin. Cultured alveolar macrophages obtained at 4 d postinjury did not have significant increases in fibronectin release. Tissue fibronectin content increased more slowly than lavage fibronectin, peaking at 4 d postinjury, and was still elevated at 7 and 14 d postinjury. Incorporation of [35S]methionine into tissue fibronectin by lung explants obtained at different times postinjury showed a similar time course. Lung collagen content increased steadily between 4 and 14 d postinjury. We conclude that, in our model, graded degrees of lung injury and fibrosis can be produced by varying the dose of unilaterally instilled paraquat and that the increases in lavage fibronectin were related mainly to capillary permeability whereas increases in tissue fibronectin represented parenchymal synthesis. The time course of changes in lung tissue fibronectin and collagen was consistent with the proposed roles of fibronectin in tissue repair and fibrosis. The ability of our model to produce graduated degrees of lung injury and fibrosis should be useful in further studies on the pathogenesis of postinjury lung fibrosis.

Albumins↗
PubMed2001

Cost effectiveness of bedside fetal fibronectin testing varies according to treatment algorithm.

OBJECTIVE: To determine the cost effectiveness of implementing fetal fibronectin testing in women with threatened preterm labor. METHODS: We developed a cost analysis model based upon our institution's experience with threatened preterm labor. Model estimates related to fetal fibronectin were obtained from the literature. The model considered hospital admission and assay cost. RESULTS: Approximately 2000 women deliver annually at our tertiary care facility. In the prior 11 months, 340 (19%) presented for threatened preterm labor with 45 (13%) admissions. In a group of individuals with threatened preterm labor and < 3 cm cervical dilatation, approximately 25% can be expected to have a positive fetal fibronectin test. If fetal fibronectin testing were used to influence the decision of admission, 93 (25%) would have a positive test over a 12-month period, potentially increasing admissions by 94%. At a cost of $225 per test, our institution's antepartum admission cost of $1919, a prevalence of threatened preterm labor of 19% and admission rate of 13%, fetal fibronectin testing applied prior to the decision to admit would result in a total cost of $262 583 with 373 assays performed, and 93 admissions. If only those who would have been admitted based on traditional criteria are considered, > 25% should have a positive fetal fibronectin test. If we assume a positive rate of 70%, fetal fibronectin testing employed after the decision to admit would result in a total cost of $75 963, with 48 assays performed and 34 admissions. Without using the assay, total costs are $92 950 for 48 admissions. CONCLUSION: This cost analysis suggests that fetal fibronectin testing on all patients presenting with threatened preterm labor significantly increases the cost, while fetal fibronectin testing after the decision to admit may reduce the cost.

Adult↗
PubMed1986

Role of fibronectin in the migration of fibroblasts into plasma clots.

The adhesion and migration of human diploid fibroblasts on plasma clots were measured. The role of plasma fibronectin was examined by depleting plasma of fibronectin before clotting. Fibronectin was not essential for cell adhesion and spreading, although rates were slightly slower on depleted clots. Rates of migration on the surface of clots were unaffected by fibronectin depletion. In contrast, fibronectin was an absolute requirement for migration of cells into plasma clots. Cells migrated rapidly into control clots but completely failed to penetrate the surface of fibronectin-depleted clots. The effect of depletion could only be reversed by adding fibronectin to depleted plasma before clotting. Adsorption of fibronectin after clotting failed to reverse the effect of depletion, suggesting that fibronectin had to be cross-linked by transglutaminase during the clotting process.

Absorption↗
PubMed1986

Coupled expression and colocalization of 140K cell adhesion molecules, fibronectin, and laminin during morphogenesis and cytodifferentiation of chick lung cells.

We have analyzed the expression and distribution of fibronectin, laminin, and the 140K cell adhesion molecules (140K complex) in embryonic chick lung cells by a combination of biochemical and immunofluorescent approaches. The 140K complex was identified by monoclonal antibody JG22E as a complex of glycoproteins averaging 140,000 Mr and has been implicated in vitro as a receptor for fibronectin and laminin. Our studies provide the first description that the 140K complex is developmentally regulated, and that the 140K complex appears to be involved in adhesion of epithelial and endothelial cells during morphogenesis. We have shown that the 140K complex is expressed in high quantity in embryonic lung cell types, but is markedly reduced in all of the differentiated cell types except smooth muscle. Embryonic lung cells are enriched in 140K complex on portions of cells in close proximity to areas rich in fibronectin. For example, during the formation of airways and alveolar tissues, 140K complex is concentrated at the basal surfaces of epithelial cells adjacent to fibronectin. Likewise, during the angiogenic invasion of capillaries into lung mesenchyme, the 140K complex becomes localized at sites on the basal surfaces of endothelial cells in close contact with fibronectin. Finally, cytodifferentiating lung smooth muscle cells show unusually high levels of 140K complex, fibronectin, and laminin that persist into the adult. In contrast to fibronectin, laminin is found to be uniformly distributed in the basement membranes of differentiating epithelial cells. It becomes prominent in adult alveolar epithelium and airway epithelium concomitant with a reduction or loss of 140K complex and fibronectin at cell-basement membrane attachment sites. Surprisingly, laminin is also present in a punctate pattern in the mesenchyme of early lung buds, however, laminin, fibronectin, and 140K complex are greatly reduced or lost during mesenchymal maturation. Our results are consistent with the active participation of the 140K complex in cell-to-matrix adhesion during morphogenesis of alveolar walls and cytodifferentiation of mesenchymal and smooth muscle cells.

Animals↗
PubMed1990

RGD-independent cell adhesion to the carboxy-terminal heparin-binding fragment of fibronectin involves heparin-dependent and -independent activities.

Cell adhesion to extracellular matrix components such as fibronectin has a complex basis, involving multiple determinants on the molecule that react with discrete cell surface macromolecules. Our previous results have demonstrated that normal and transformed cells adhere and spread on a 33-kD heparin binding fragment that originates from the carboxy-terminal end of particular isoforms (A-chains) of human fibronectin. This fragment promotes melanoma adhesion and spreading in an arginyl-glycyl-aspartyl-serine (RGDS) independent manner, suggesting that cell adhesion to this region of fibronectin is independent of the typical RGD/integrin-mediated binding. Two synthetic peptides from this region of fibronectin were recently identified that bound [3H]heparin in a solid-phase assay and promoted the adhesion and spreading of melanoma cells (McCarthy, J. B., M. K. Chelberg, D. J. Mickelson, and L. T. Furcht. 1988. Biochemistry. 27:1380-1388). The current studies further define the cell adhesion and heparin binding properties of one of these synthetic peptides. This peptide, termed peptide I, has the sequence YEKPGSP-PREVVPRPRPGV and represents residues 1906-1924 of human plasma fibronectin. In addition to promoting RGD-independent melanoma adhesion and spreading in a concentration-dependent manner, this peptide significantly inhibited cell adhesion to the 33-kD fragment or intact fibronectin. Polyclonal antibodies generated against peptide I also significantly inhibited cell adhesion to the peptide, to the 33-kD fragment, but had minimal effect on melanoma adhesion to fibronectin. Anti-peptide I antibodies also partially inhibited [3H]heparin binding to fibronectin, suggesting that peptide I represents a major heparin binding domain on the intact molecule. The cell adhesion activity of another peptide from the 33-kD fragment, termed CS1 (Humphries, M. J., A. Komoriya, S. K. Akiyama, K. Olden, and K. M. Yamada. 1987. J. Biol. Chem., 262:6886-6892) was contrasted with peptide I. Whereas both peptides promoted RGD-independent cell adhesion, peptide CS1 failed to bind heparin, and exogenous peptide CS1 failed to inhibit peptide I-mediated cell adhesion. The results demonstrate a role for distinct heparin-dependent and -independent cell adhesion determinants on the 33-kD fragment, neither of which are related to the RGD-dependent integrin interaction with fibronectin.

Amino Acid Sequence↗
PubMed1996

Beta 1 integrin-dependent and -independent polymerization of fibronectin.

The mouse cell line GD25, which lacks expression of the beta 1 family of integrin heterodimers due to disruption of the beta 1 integrin subunit gene, was used for expression of full-length cDNA coding for splice variant A of the mouse beta 1 integrin subunit. In a stably transformed clone (GD25-beta 1A), the expressed protein was found to form functional heterodimeric receptors together with the subunits alpha 3, alpha 5, and alpha 6. Both GD25 and GD25-beta 1A attached to fibronectin and formed focal contacts which contained alpha v beta 3, but no detectable alpha 5 beta 1A. The presence of GRGDS peptide allowed alpha 5 beta 1A to locate to focal contacts of GD25-beta 1A cultured on fibronectin, while the beta 1-null GD25 cells were unable to attach under these conditions. Affinity chromatography revealed that alpha 5 beta 1A and alpha v beta 3 could bind to a large cell-binding fragment of fibronectin. alpha 5 beta 1A strongly promoted polymerization of fibronectin into a fibrillar network on top of the cells. Whereas little alpha v beta 3 was colocalized with the fibronectin fibrils in GD25-beta 1A cells, this integrin was able to support fibronectin fibril polymerization in GD25 cells. However, the alpha v beta 3-induced polymerization was less efficient and occurred mainly in dense cultures of the GD25 cells. Thus, while both alpha 5 beta 1A and alpha v beta 3 are able to support adhesion to fibronectin, alpha v beta 3 dominates in the formation of focal contacts, and alpha 5 beta 1A has a prime function in fibronectin matrix assembly. This is the first report on fibronectin matrix assembly in the absence of beta 1 integrins.

Animals↗
PubMed1983

Fibronectin expression during myogenesis.

The biosynthesis and localization of fibronectin during chick muscle differentiation are described. This study employed two monoclonal antibodies, one that selectively killed mononucleated cells and one specific for avian fibronectin. These antibodies allowed precise analyses of fibronectin expression in well-defined cultures of myoblasts or myotubes and avoided the complications of exogenous fibronectin and contamination by fibroblasts or unfused myoblasts. Fibronectin synthesis, as a fraction of total protein synthesis, remains constant at 0.3-0.4% before and after myoblast fusion, suggesting that the absolute rate of fibronectin synthesis may increase somewhat when myotubes synthesize and accumulate myofibrillar proteins. The pattern of fibronectin arrangement does change during myogenesis. In myotube cultures, the appearance of pulse-labeled fibronectin at the cell surface and its secretion into the medium begin after a 2-3-h lag period, in contrast to the 30-min lag period observed in fibroblast cultures. This lag between polypeptide biosynthesis and the exteriorization of the new protein is thus a characteristic of each cell type rather than the protein. All of the major secretory proteins of myogenic cells, including fibronectin and collagenous components, share this 2-3-h intracellular transit time.

Animals↗
PubMed1984

Expression of transformation-associated protease(s) that degrade fibronectin at cell contact sites.

Virus-transformed fibroblasts show an increased production of proteases as well as loss of extracellular adhesive proteins. To determine whether these transformation-associated events are related, we investigated the capacity of Rous sarcoma virus-transformed cells (embryonic chick fibroblasts and mouse BALB/c 3T3) to degrade fibronectin by using a novel cross-linked protein substratum: fluorescence-labeled or radiolabeled fibronectin covalently linked to the surface of a fixed gelatin film. In serum-containing medium, the coupled fibronectin was not released when incubated without cells, and only a small amount was released when incubated with nontransformed cells. However, when transformed cells were seeded on the radiolabeled fibronectin-coupled substratum, there was a threefold increase in the time-dependent release of radioactivity into the medium. The released material was characterized as peptides with molecular sizes of less than 30,000 daltons. Correspondingly, growth of transformed cells on the rhodamine-fibronectin substratum resulted in the appearance of discrete negative fluorescent spots beneath the cells and along their migratory paths, whereas a uniform fluorescent carpet was detected with nontransformed cells. The release of radioactivity was partially inhibited by protease inhibitors, including alpha 2-macroglobulin, leupeptin, and benzamidine, but the negative fluorescent spots appeared unaffected by any of these inhibitors. However, both the release of radiolabeled peptides and the appearance of fluorescence-negative spots were inhibited by 1,10-phenanthroline at concentrations that did not affect cellular attachment and protein synthesis, thus supporting a role for proteases in localized degradation of fibronectin substratum. These fluorescence-negative spots coincided with sites of fibronectin disappearance as judged by indirect labeling with antibodies to cellular fibronectin. In addition, immunofluorescent analyses showed a correlation between vinculin localization and the negative fibronectin spots found under transformed cells, indicating that degradation occurs at cell substratum contact sites. These results can be correlated with other transformation-associated phenotypic changes, and are discussed in terms of the invasion of tumor cells into the extracellular matrix.

Animals↗
PubMed1984

In vivo co-distribution of fibronectin and actin fibers in granulation tissue: immunofluorescence and electron microscope studies of the fibronexus at the myofibroblast surface.

The fibronexus ( FNX ), a very close transmembrane association of individual extracellular fibronectin fibers and actin microfilaments, was found previously at the substrate-binding surface of fibroblasts in tissue culture (Singer, 1. 1., 1979, Cell, 16:675-685). To determine whether the fibronexus might be involved in fibroblast adhesion during wound healing in vivo, we looked for co-localization of actin and fibronectin in granulation tissue formed within full-thickness guinea pig skin wounds. At 7-9 d, most of the actin fibers were observed to be coincident with congruent fibronectin fibers using double-label immunofluorescence microscopy. These fibronectin and actin fibers were co-localized at the myofibroblast surface surrounding the nucleus, and along attenuated myofibroblast processes which extended deeply into the extracellular matrix. This conspicuous co-distribution of fibronectin and actin fibers prompted us to look for fibronexuses at the myofibroblast surface with electron microscopy. We observed three kinds of FNXs : (a) tandem associations between the termini of individual extracellular fibronectin fibers and actin microfilament bundles at the tips of elongate myofibroblast processes, (b) plaque-like and, (c) track-like FNXs , in which parallel fibronectin and actin fibers were connected by perpendicular transmembranous fibrils. Goniometric studies on the external and internal components of these cross-linking fibrils showed that their membrane-associated ends are probably co-axial. Using immunoelectron microscopy on ultrathin cryosections, we confirmed that the densely staining external portion of these various FNXs does indeed contain fibronectin. The finding that these FNXs appear to connect collagen fibers to intracellular bundles of actin microfilaments is particularly significant. Our studies strongly suggest that the fibronexus is an important in vivo cell surface adhesion site functioning in wound repair, and perhaps within fibronectin-rich tissues during embryogenesis, tumor growth, and inflammation.

Actins↗
PubMed1995

Distribution of fibronectin-binding proteins among group A streptococci of different M types.

Binding of fibronectin by group A streptococci (GAS) promotes adherence to epithelial cells. The fibronectin-binding activity and the presence of prtF, a gene encoding a fibronectin-binding protein, were studied among 109 strains. Fifty-six strains of 42 different M types possessed prtF-related genes, and 89% of these strains bound fibronectin at high levels. The prtF-related genes varied in the number of repeats that constitute one of its two fibronectin-binding domains. Fifty-three strains of 21 different M types lacked prtF. Thirty-nine of these (74%), representing 13 different M types, bound fibronectin at very low levels. However, 9 (17%), of 5 different M types, bound fibronectin at high levels. The presence of prtF and the capacity to bind fibronectin correlated strongly with the M type of various strains of GAS. This correlation may suggest the existence of a relationship between fibronectin binding and the pathogenic potential of GAS.

Adhesins, Bacterial↗
PubMed2000

Cytotoxic effects of tumour necrosis factor (TNF)-alpha and interferon-gamma on cultured human trophoblast are modulated by fibronectin.

Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma, produced by maternal inflammatory cells, may compromise trophoblast survival at the trophoblast-maternal interface and notably in the placental bed which is invaded by trophoblast. Extracellular matrix components, e.g. fibronectin, may enhance trophoblast survival. A possible protective effect of fibronectin against toxic effects of TNF-alpha and IFN-gamma was investigated in cultured trophoblasts isolated from six human term placentas, grown on uncoated and fibronectin-coated plastics. IFN-gamma and increasing doses of TNF-alpha resulted in decreasing viability of trophoblast on uncoated as well as fibronectin-coated dishes, as shown by 3-[4, 5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assays, but for each TNF/IFN treatment condition viability on fibronectin was higher (P < 0.001). Epidermal growth factor (EGF), a growth factor reported to protect against TNF-alpha/IFN-gamma induced toxicity, resulted in further increased viability, but not if IFN-gamma was included in the treatment. EGF caused increased fibronectin secretion into the medium (P < 0.001), and double cytokeratin/fibronectin immunostaining confirmed the trophoblastic nature of fibronectin secreting cells. We conclude that fibronectin increases viability, but does not completely abolish the cytotoxic action of TNF-alpha and IFN-gamma on trophoblast. The protective effect of EGF may be related to stimulation of fibronectin secretion by trophoblast.

Cell Survival↗