Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:009431 (fibronectin)
 32,104 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently shown that monolayer cultures of calf pulmonary artery endothelial (CPAE) cells pretreated with phorbol myristate acetate (PMA) generate a conditioned medium that is chemotactic for human polymorphonuclear leucocytes (PMNL). Fibronectin (Fn) is a multidomain protein found in the plasma and subendothelial extracellular matrix that induces attachment and migration of a variety of cell types. The present study was designed to evaluate the role of Fn or fragments of Fn present in conditioned medium from phorbol ester-stimulated endothelial cells as potential chemotactic factors for human PMNL. A large number of Fn fragments were revealed by Western immunoblotting of serum-free conditioned medium 4 hr after treatment of CPAE monolayers with PMA. Gelatin-Sepharose affinity chromatography of 4-hr conditioned medium demonstrated chemotactic activity for PMNL in both gelatin-binding and non-gelatin-binding fractions. The addition of bovine Fn antiserum to the conditioned medium inhibited PMNL chemotaxis in a dose-dependent manner while having no effect on PMNL chemotaxis generated by zymosan-activated serum. One site on the Fn molecule known to interact with phagocytic cells is the cell-binding domain containing the Arg-Gly-Asp (RGD) sequence. Pretreatment of PMNL with a RGD-containing peptide (1 mM GRGDSPK) for 10 min completely inhibited the expression of chemotactic activity present in conditioned medium and in the gelatin-binding and non-gelatin-binding fractions. PMNL chemotaxis was not stimulated by either intact Fn or the RGD-containing septapeptide tested over a wide concentration range. However, incubation of PMNL with a purified 120,000-MW fragment of Fn containing the cell-binding domain stimulated chemotaxis in a dose-dependent manner. In contrast, a purified 45,000 MW fragment of Fn containing the gelatin-binding domain was not chemotactic for PMNL. When a monoclonal antibody directed against the cell-binding domain of Fn was incubated with conditioned medium, a significant reduction in PMNL chemotaxis was observed. These results demonstrate that phorbol ester-stimulated pulmonary artery endothelial cells release Fn fragments and suggest an important role for Fn fragments containing the cell-binding domain in stimulating the migration of PMNL.
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PMID:Fibronectin fragments released from phorbol ester-stimulated pulmonary artery endothelial cell monolayers promote neutrophil chemotaxis. 193 65

Human peripheral blood neutrophils were exposed in vitro, in a tonometer, to two different fractions of cigarette smoke-designated particulate phase and vapor phase. The proteolytic activity of the cells following exposure was assessed by measuring their elastase release and ability to degrade fibronectin. At levels of smoke exposure that were physiologically attainable, neither smoke fraction caused an increase in elastase release or fibronectin degradation. In most experiments, fibronectin proteolysis was suppressed by smoke exposure--an effect that was reversible on treatment with phorbol myristate acetate. These data provide evidence that the proteolytic activity of neutrophils is not enhanced by a direct effect of cigarette smoke on these cells.
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PMID:Reduction of the proteolytic activity of neutrophils by exposure to cigarette smoke in vitro. 195 3

Rous sarcoma virus-transformed rat liver cell line RSV-BRL secreted a neutral proteinase in a latent precursor form with a molecular weight (Mr) of 57,000 (57k) as a major secreted protein. This enzyme was a calcium-dependent metallo-proteinase. The proenzyme was purified from the serum-free conditioned medium of the transformed cells by affinity chromatographies on a zinc chelate Sepharose column and a reactive red agarose column. When activated by treatment with trypsin or p-aminophenylmercuric acetate (APMA) in the presence of Ca2+, the purified enzyme effectively hydrolyzed casein, fibronectin, and laminin. Type IV collagen was hydrolyzed at 37 degrees C but not at 30 degrees C by the enzyme, whereas type I and type III collagens were hardly hydrolyzed even at 37 degrees C. The treatment with trypsin or AMPA in the presence of Ca2+ converted this 57k proenzyme to an active and stable enzyme with Mr 42k. In the absence of Ca2+, however, APMA converted the proenzyme to an intermediate form with Mr 45k, while trypsin digested it to an inactive peptide with Mr 30k. These results demonstrate that calcium ion is essential for the activation, activity expression, and stabilization of this metallo-proteinase. Analysis of its partial amino acid sequence and amino acid composition showed that the 57k proenzyme was identical or closely related to the putative protein transin, a rat homologue of stromelysin.
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PMID:Purification and properties of extracellular matrix-degrading metallo-proteinase overproduced by Rous sarcoma virus-transformed rat liver cell line, and its identification as transin. 196 30

The Arg-Gly-Asp (RGD) tripeptide and ajoene were used for studying the role of adhesive receptors in the respiratory burst. Activation of the respiratory burst was examined by using luminol-dependent and lucigenin-dependent chemiluminescence. Recently, it was shown that ajoene, (E, Z)-4,5,9-trithiadodeca-1,6,11-trien-9-oxide, a substance isolated from garlic extract, inhibits the binding of fibrinogen to activated platelets by direct interaction with fibrinogen receptor (Apitz-Castro, R., Lederma, E., Escalante, J. and Jain, M.K. (1986) Biochem. Biophys. Res. Commun. 141, 145-150). Taking into consideration the structural and functional similarity of integrins, it would be reasonable to assume that ajoene as well as RGD can inhibit adhesive interactions of human neutrophils. We have shown that the effect of various activators on the respiratory burst was abolished by ajoene or RGD treatment. The inhibitory effect of RGD and ajoene was dose-dependent. The treatment of neutrophils with antiserum against human plasma fibronectin inhibited the respiratory burst in response to formyl-methionyl-leucylphenylalanine (fMLP) and phorbol 12-myristate 13-acetate (PMA). This effect is dose-dependent and reversible with the addition of fibronectin. These data indicate that the respiratory burst in human neutrophils is mediated by the integrin family of receptors and that interactions between the extracellular matrix fibronectin and cells are necessary for the respiratory burst.
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PMID:The role of adhesive interactions and extracellular matrix fibronectin from human polymorphonuclear leukocytes in the respiratory burst. 200 8

Cell-matrix interactions play an important role in the maintenance of cell shape, supposed to be mediated by the anchorage of cellular cytoskeleton to extracellular matrix via matrix receptors. In this work the expression of one of the known matrix receptors, syndecan, was studied during the hormone-induced change in the phenotype of Shionogi 115 (S115) mouse mammary tumor cells. In the presence of testosterone, when S115 cells express fibroblastic phenotype, they increased their growth rate and became gradually anchorage independent. These cells, however, revealed strong RGDS-dependent binding to fibronectin (FN) but not binding to the heparin-binding domain of FN. Instead, S115 cells growth without testosterone showed epithelial morphology and binding to the heparin-binding domain of FN, suggesting an alteration of syndecan expression in hormone-treated S115 cells. As quantitated by radioimmunoassay and by Western blot, the amounts of both matrix-binding ectodomain of syndecan and syndecan mRNA (2.6 kb) declined in hormone-treated S115 cells. The addition of antiandrogen cyproterone acetate to culture medium opposed the effect of testosterone on syndecan mRNA. We thus propose that the inactivation of syndecan gene and the consequent suppression of syndecan expression is related to the altered adhesion properties, the disappearance of epithelial phenotype, and, on the other hand, to the appearance of transformed-like phenotype in hormone-treated S115 cells.
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PMID:Steroid-induced epithelial-fibroblastic conversion associated with syndecan suppression in S115 mouse mammary tumor cells. 200 84

Stimulation of cells with protein kinase C (PKC)-specific activators such as phorbol esters increased in a reversible manner the rate of adherence of [3H]leucine-labelled L1210 cells to cultured bovine cerebral cortex capillary endothelial cells (CEC). This effect was not specific for L1210 cells since 12-O-tetradecanoyl phorbol 13-acetate (TPA) strongly increased the binding of various other tumor cell lines. Phorbol esters increased the rate of L1210 cell adhesion to CEC by enhancing their binding capacity without affecting the apparent affinity of L1210 cells for CEC. This stimulation was specific to the phorbol analogs which activate PKC since it was not effected by 4 alpha-phorbol didecanoate, known to be inactive for PKC. Down-regulation experiments showed that adhesion enhancement was entirely attributable to an effect on tumor cells without contribution of CEC intracellular PKC. PKC inhibitors like staurosporine, sphingosine and H-7 showed strong antagonistic activity towards TPA-induced L1210 cell adherence to CEC (IC50 = 0.5 nM, 160 nM and 10 microM, respectively). Adhesive proteins such as vitronectin, fibrinogen, fibronectin and the tetrapeptide RGDS, an active sequence from their cell-binding domains, exhibited potent, dose-dependent inhibition of PKC-induced tumor cell adhesion.
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PMID:Tumor cell adherence to cultured capillary endothelial cells is promoted by activators of protein kinase C. 206 89

Increased fibroblast growth-stimulating activity (FGA) was found in bronchoalveolar lavage fluid (BALF) from sarcoidosis patients. For evaluation of the significance of FGA in disease activity and the pathophysiology of sarcoidosis, the FGA levels were compared with data on cellular analysis of BALF, serum angiotensin-converting enzyme (S-ACE) activity and chest radiograms. The FGA level was significantly higher in sarcoidosis patients with parenchymal involvement (radiological stages II and III) than in those without parenchymal involvement (radiological stage I). The FGA was positively correlated with albumin and fibronectin concentrations in BALF. However, it was not significantly correlated with the ratio of CD-4 + to CD-8 + T-lymphocytes in BALF or the S-ACE level, which are known to be useful in evaluating the disease activity of sarcoidosis. These results indicate that the diagnostic value of FGA is different from that of the lymphocyte subpopulations in BALF and S-ACE, and is useful in estimating the extent of parenchymal involvement in sarcoidosis.
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PMID:Fibroblast growth-stimulating activity in bronchoalveolar lavage fluid of patients with pulmonary sarcoidosis. 210 7

Serum-free mouse embryo cells cultured in medium supplemented with insulin, transferrin, high-density lipoprotein, and fibronectin are dependent on epidermal growth factor for survival. Cycloheximide or actinomycin D prevented cell death caused by growth factor deprivation, suggesting that cell death required the synthesis of RNA and protein, a phenomenon similar to that reported for neuronal cell death in the absence of nerve growth factor. Orthovanadate, an inhibitor of phosphotyrosine phosphatases, and 12-O-tetradecanoylphorbol-13-acetate, an activator of protein kinase C, also prevented serum-free mouse embryo cell death in the absence of epidermal growth factor.
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PMID:Death of serum-free mouse embryo cells caused by epidermal growth factor deprivation is prevented by cycloheximide, 12-O-tetradecanoylphorbol-13-acetate, or vanadate. 215 51

The primary focus of this experiment was on the investigation of localizations of alpha 1-antitrypsin (alpha 1-AT), alpha 1-antichymotrypsin (alpha 1-ACT), fibronectin (FN) and lysozyme (LY) in tumor cells of experimental malignant fibrous histiocytoma (MFH). The induction of MFH was conducted by injecting Fischer 344 rats with 4-hydroxyaminoquinoline 1-oxide (4-HAQO). In 46 out of 50 rats, tumors were generated, all of which were diagnosed as MFH and classified into 5 subtypes, according to their histological properties. The presence of alpha 1-AT, alpha 1-ACT and FN in all MFH tumor cells was observed in the tumor cells of various types. Especially, fibroblast-like, histiocyte-like and Touton and/or Epulis type giant cells showed strong reactivity. However, positive reaction of LY in MHF tumor cells was very weak, or the reaction was negative. These findings are consistent with those of human MFH.
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PMID:Immunohistochemical study of 4-hydroxyaminoquinoline 1-oxide-induced rat malignant fibrous histiocytoma. 215 61

The structure of the gene for human 70-kDa type IV collagenase (gelatinase) was determined. Three overlapping genomic clones were isolated and shown to contain 0.4 kilobase (kb) of the 5'-flanking region, the 27-kb structural gene, and 4.5 kb of the 3'-flanking region. The gene has 13 exons that vary in length from 110 to 901 base pairs (bp) and 12 introns that range from 175 to 4350 bp. Alignment of intron locations demonstrated that introns 1-4 and 8-12 of the type IV collagenase gene coincide with intron locations in the interstitial collagenase and stromelysin genes, indicating a close structural relationship of these metalloproteinase genes. Exons 5-7 are each 174 bp in size, and each codes for one complete internal repeat that resembles the collagen-binding domains of fibronectin. The transcription initiation site was determined by primer extension and S1 nuclease analyses. Analysis of the 0.4-kb 5'-flanking region of the gene showed that, in contrast to the genes of interstitial collagenease and stromelysin, there is no TATA box or 12-O-tetradecanoylphorbol-13-acetate-responsive element present in the promoter region, whereas there are two GC boxes. There is no CAAT box, but a potential binding site (CCCCAGGC) for the transcription factor AP-2 is located in the first exon.
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PMID:Structure of the human type IV collagenase gene. 216 31


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