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)

Fibronectin (Fn), which is released from several kinds of cells including alveolar macrophages (AM), is important in inflammatory reactions in the certain lung diseases such as idiopathic pulmonary fibrosis (IPF). Therefore, information on the mechanisms regulating Fn release from AM may be useful for elucidating the pathogenesis of these diseases and developing therapeutic modalities. We supposed that prostaglandin E2 (PGE2), which is known to modulate cellular functions, might be involved in regulation of Fn release, and, accordingly, we measured the release of Fn and PGE2 from AM from normal volunteers (NV), control patients (CP), and patients with IPF. AM from patients with IPF were found to release more Fn than AM from NV (IPF: 250 +/- 58.8/10(6) cells.24 h, NV: 53.0 +/- 7.3 ng/10(6) cells.24 h) and to release less PGE2 than the latter (IPF: 0.48 +/- 0.12 ng/10(6) cells.24 h, NV:1.35 +/- 0.24 ng/10(6) cells.24 h). A negative correlation was found between the contents of Fn and PGE2 in the culture media of AM from NV, CP, and patients with IPF. Lipopolysaccharide, phorbol myristate acetate, and zymosan suppressed Fn release from AM but stimulated their PGE2 release, and these effects were reversed by indomethacin. Exogenous PGE2 (greater than 1 x 10(-8) M) suppressed Fn release. The albumin-antialbumin complex stimulated Fn release but did not affect PGE2 release. These results indicate that Fn release from AM changed in response to various stimuli, and that PGE2 is important in suppressing Fn release from AM, suggesting a negative feedback mechanism of PGE2 in releasing Fn.
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PMID:Regulatory effect of prostaglandin E2 on fibronectin release from human alveolar macrophages. 232 58

It was found out that macrophage superoxide production is stimulated by intracellular contacts. The high level of the nitro-blue tetrazolium salt reduction in individual cells non-contacting with others is reached when using fibronectin or serum-opsonized zymosan but not phorbol myristate acetate or chemotactic formyl-peptide as activators. The reaction enhancement in non-contacting macrophages stimulated with phorbol ester occurs in the presence of Arg-Gly-Asp-Ser synthetic peptide.
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PMID:[Role of intracellular contact interactions in macrophage reaction to activators containing and not containing the Arg-Gly-Asp sequence]. 233 63

Recently, we have shown that transformation of human keratinocytes by SV40 virus induces the re-expression of characters found in fetal epidermis and monostratified epithelia. In the present study, TPA was found to alter some features of the human keratinocyte phenotype in a similar manner to SV40 transformation. Indeed, 12-O-tetradecanoyl-13-phorbol acetate (TPA) treatment induced the expression of cytokeratin no. 8, recognized by the monoclonal antibody TROMA-1, which is present in fetal epidermis and/or monostratified epithelia only, and fibronectin expression. However, TPA and SV40 transformation had specific non-overlapping effects. For example, TPA did not prevent terminal differentiation and stratification, as SV40-transformation did, but stimulated these processes. Moreover, TPA was found to induce additional changes in SV40-transformed keratinocytes. In particular it provoked the individualization of cells within the colonies. This effect was seen as little as 1 h after treatment and was reversible. This cellular alteration was accompanied by the reorganization of actin and by a decrease in the number of desmosomes; these changes were not observed after treatment of normal keratinocytes with TPA. These observations lead to the conclusion that TPA is able to trigger cellular responses which cannot be induced by SV40 products alone, but that TPA and some SV40 products can cooperate to elicit new responses, which could reflect a higher state of malignancy.
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PMID:Transformation of human keratinocytes by SV40 virus alters their response to the tumor promoter TPA. 242 37

Standard cytological and histological staining procedures were successfully applied on nitrocellulose (NC) paper for staining a spectrum of cell types that were blotted on it. The staining procedures included a Papanicolaou method, a hematoxylin and eosin method, and an immunoperoxidase technique. The cell types consisted of various suspension and monolayer cultures as well as cells freshly prepared from tumor and nontumor tissues. Suspended cells were manually blotted on NC paper; they were fixed in one of the fixatives, which included 80% 2-propanol, 10% neutral-buffered formalin, Carnoy's solution, Bouin's fluid, and B-5 fixative; they were then stained by one or more of the above methods. After staining, the NC paper was dehydrated in absolute 2-propanol; made transparent by soaking in xylene; mounted permanently in a mounting medium (Permount) on a glass slide; and then examined under a microscope. The protein-blotting capacity of NC paper (Schleicher & Schuell) was compared with those of the conventional cell blotting media (Millipore and Gelman) which contained cellulose acetate. Bovine serum albumin was dot-blotted on the NC and the cellulose acetate filters, and stained for protein by amido black. As in cytological/histological staining, the amido black-stained filters were dehydrated in absolute 2-propanol, made transparent in xylene, and mounted in Permount. Densitometric tracings indicated that the NC paper bound the highest amount of protein. The feasibility of cytological/histological staining techniques on NC paper combined with its high protein-blotting capacity allowed in situ staining and microscopical characterization of baby hamster kidney cells binding to fibronectin blotted on the NC paper. The possible significance of these techniques in current cell biological research was discussed.
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PMID:Cell blotting: techniques for staining and microscopical examination of cells blotted on nitrocellulose paper. 243 Apr 87

Recombinant tumor necrosis factor alpha (rTNF alpha) and beta (rTNF beta) did not trigger H2O2 release from PMN in suspension. However, when PMN were plated on polystyrene surfaces coated with serum, fibronectin, vitronectin, laminin, or human umbilical vein endothelial cells (HUVEC), rTNFs induced a massive, prolonged secretory response, similar to that elicited by phorbol myristate acetate (PMA) or bacteria. On serum-coated plates, the maximum sustained rate of H2O2 release in response to rTNF alpha was 2.6 +/- 0.2 nmol/min per 10(6) PMN, the same as that with PMA; release continued for 73 +/- 4 min. On laminin-coated surfaces or HUVEC, release of H2O2 in response to rTNFs was slower, but lasted approximately 3.5 h, reaching the same total (greater than 100 nmol/10(6) PMN). Not only was this response far longer and larger than for other soluble stimuli of the respiratory burst studied with PMN in suspension, but the concentration necessary to elicit a half-maximal response (EC50) for rTNF alpha was orders of magnitude lower (55 pM). Responses were similar with FMLP, but ranged from zero to small with recombinant IFN alpha, recombinant IFN beta, recombinant IFN gamma, platelet-derived growth factor, recombinant IL-1 beta, or bacterial lipopolysaccharide. Adherent monocytes did not secrete H2O2 in response to rTNFs. H2O2 secretion by adherent PMN was first detectable 15-90 min after addition of rTNFs or FMLP. This lag period was unaffected by prior exposure of PMN to rTNF alpha in suspension, by allowing PMN to adhere before adding rTNF alpha, or by incubating adherent PMN in medium conditioned by rTNF alpha-treated PMN. Cytochalasins abolished H2O2 secretion in response to rTNFs, but not FMLP, if added during, but not after, the lag period. Thus, H2O2 secretion from rTNF alpha-treated PMN appears to be a direct but delayed response that requires assembly of microfilaments during exposure to the cytokine. These results suggest that PMN adherent to intra- or extravascular surfaces may undergo a massive, prolonged respiratory burst at the command of macrophages and lymphocytes reacting to microbial products and antigens.
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PMID:Neutrophil activation on biological surfaces. Massive secretion of hydrogen peroxide in response to products of macrophages and lymphocytes. 244 80

The effect of differentiation induction by a tumor-promoting phorbol diester, 12-O-tetradecanoylphorbol-13-acetate (TPA) on a clonal human megakaryoblastic cell line, MEG-O1s, was investigated, and a prominent response was demonstrated. The cells became weakly adherent, developed conspicuous cytoplasmic blebs, and displayed mature megakaryocytic characteristics by light microscopy such as the development of azurophilic cytoplasmic granules and a mosaic pattern of oxyphilic patches, multiplication of nuclei, and enhancement of the PAS reaction and alpha-naphthyl acetate esterase staining. Ultrastructural studies demonstrated the development of prominent cytoplasmic blebs, budding of blebs, and multiplication of nuclei. Numerous granules with central nucleoids that are similar to alpha granules had developed as well as granules with high electron density and clearly demarcated zones. Surface marker analysis revealed a moderate increase in IgG Fc receptor levels and a profound decrease in C3 receptor sites. By an immunofluorescent technique using monoclonal and polyclonal antibodies, a dramatic change in the expression of several megakaryocyte-platelet-specific proteins was demonstrated. All the proteins that had been expressed before induction such as platelet glycoprotein (GP) IIb/IIIa, fibrinogen, von Willebrand factor, factor XIIIA, beta-thromboglobulin (beta-TG), and HLA class 1 antigen were profoundly enhanced after induction by TPA. Induction by TPA led to the expression of fibronectin and factor V, which were not detected on nontreated cells. An ultrastructural immunoperoxidase study demonstrated platelet GPIb and GPIIb/IIIa in both plasma membranes and protein synthesis areas such as perinuclear cisternae and endoplasmic reticulum after TPA induction. beta-TG was also observed in some cytoplasmic granules of TPA-treated cells. TPA remarkably increased the secretion of beta-TG into the culture medium of MEG-01s. Ploidy was also increased from 2C to 4C to 4C to 8C. Similar maturation of MEG-01s was induced by other phorbol diester analogues such as phorbol-12,13-dibutyrate, but not by phorbol itself. These results indicate that phorbol diester, TPA, can bring about differentiation and maturation of a human megakaryoblastic cell line (MEG-01s) and that MEG-01s cells will provide a useful model for studying megakaryocytic differentiation and numerous megakaryocyte-platelet-specific proteins.
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PMID:Functional and morphological differentiation induction of a human megakaryoblastic leukemia cell line (MEG-01s) by phorbol diesters. 245 75

Mac-1 (CD 11b/CD18) is a leukocyte adhesion heterodimeric glycoprotein which functions both as a receptor for iC3b (CR3) and in several cell-cell and cell-substrate adhesive interactions. We describe full-length cDNA clones for the alpha subunit of Mac-1. Mac-1 alpha subunit message was detected in blood monocytes and phorbol-12-myristate acetate-induced myeloid cell lines, but not in cells of the T or B lineages, correlating with Mac-1 protein surface expression. The alpha subunit of Mac-1 is a transmembrane protein of 1137 residues with a long extracellular domain (1092 residues) and a 19-amino acid cytoplasmic tail. The extracellular domain contains three putative divalent cation-binding sequences and 19 potential N-glycosylation sites. The amino acid sequence of Mac-1 alpha shows that it is a member of the integrin superfamily; Mac-1 alpha shows 63% identity to the alpha subunit of the leukocyte adhesion glycoprotein p150.95 and 25% to the alpha subunits of the extracellular matrix receptors platelet glycoprotein IIb/IIIa, the fibronectin receptor, and the vitronectin receptor. The Mac-1 alpha subunit putative divalent cation-binding sites and the flanking regions exhibit a high degree of identity both to the p150.95 alpha subunit (87% identity at the amino acid level) and to the rest of the integrin alpha subunits (38%). The alpha subunit of Mac-1, like the p150.95 alpha subunit, contains a domain of 187 amino acids in the extracellular region which is absent in other integrins. This leukocyte or "L" domain is homologous to the A domains of von Willebrand factor, which in turn are homologous to regions of the C3-binding proteins factor B and C2. These findings draw attention to this region of Mac-1 as a potential binding site for iC3b.
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PMID:The human leukocyte adhesion glycoprotein Mac-1 (complement receptor type 3, CD11b) alpha subunit. Cloning, primary structure, and relation to the integrins, von Willebrand factor and factor B. 245 84

Thyrotropin-releasing hormone (TRH) and epidermal growth factor both enhance prolactin synthesis and substrate adhesion (a morphological change called stretching) of GH4 rat pituitary cells. We have examined TRH- and EGF-induced cell stretching using genetic and pharmacologic approaches. We selected and isolated a series of GH4 cell variants nonresponsive to TRH-induced cell stretching (str-). This selection yielded several variants that were nonresponsive to both TRH- and EGF-induced stretching but were still responsive to stretching induced by several other agents (tetradecanoylphorbol acetate [TPA], butyrate, and Neplanocin A). One of the str- variants (a14) was examined in detail. TRH, EGF, and TPA each enhanced prolactin synthesis in a14 cells, indicating that the a14 variant contained functional receptor binding sites for all 3 ligands as well as the capacity to generate those intracellular signals required for enhanced prolactin synthesis. Because the str- variants were isolated without selective pressure for EGF-induced stretching and because the possibility of more than one selectable mutation in all the variants is unlikely, we suggest that TRH and EGF share a common mechanism to induce cell stretching. We next examined whether the str- variants had a defect in a signaling pathway or in the biochemical endpoint for TRH- and EGF-induced cell stretching. A pharmacologic approach was utilized to investigate the biochemical basis for induced cell stretching. A synthetic Arg-Gly-Asp-Ser tetrapeptide (RGDS), specific for fibronectin and vitronectin adhesion receptors, inhibited TRH-, EGF-, and TPA-induced GH4 cell stretching and attachment to fibronectin- and vitronectin-coated dishes. These results suggest that the interaction between fibronectin and/or vitronectin and their receptor(s) may be a biochemical endpoint by which several agonists induced stretching of GH4 cells. Because the str- variant has RGDS-specific binding sites for fibronectin and vitronectin and responds to some agents that induce cell stretching via an RGDS receptor, we conclude that the a14 str- variant has a defect in an intracellular signaling pathway, shared by TRH and EGF, which induces cell stretching.
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PMID:GH4 pituitary cell variants selected as nonresponsive to thyrotropin-releasing hormone-enhanced substratum adhesion are nonresponsive to epidermal growth factor: evidence for a common signaling defect. 248 Mar 54

The differentiation inducing effect of coated human fibronectin (HFN) on U937 was investigated. U937 cells usually proliferate without stimuli. HFN induced the adhesion of about 20% of U937 cells in a serum free medium. HFN did not inhibit cell growth nor induce CD14 expression. The adhesion inducing activity of HFN was completely blocked by addition of anti-HFN antibody. Phorbor 12-myristate 13-acetate (PMA), another differentiation inducing agent, inhibited the growth of U937 cells but did not induce adhesion in the serum free medium. These data imply that HFN has a differentiation inducing effect on a human monocytic cell line and could be used as a biological response modifier.
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PMID:Coated fibronectin induces adhesion in the human monocytic cell line U937. 248 55

Lewis lung carcinoma cells express a plasma membrane receptor (i.e., IRGpIIb/IIIa) which is immunologically and functionally related to the platelet aggregation receptor complex (i.e., GpIIb/IIIa). Both fluorescence microscopy and flow cytometric analysis reveal that surface expression and/or activation of this tumor cell receptor is enhanced by a phorbol ester [i.e., 12-O-tetradecanoylphorbol-13-acetate (TPA)] and a lipoxygenase metabolite of arachidonic acid; 12-hydroxyeicosatetraenoic acid (i.e., 12-HETE). TPA-enhanced expression appears to be mediated by a lipoxygenase metabolite, as this effect can be reversed by lipoxygenase inhibitors but not by cyclooxygenase inhibitors. In parallel with these results both TPA and 12(S)-HETE [but not 12(R)-HETE] enhance tumor cell adhesion to endothelial cells, subendothelial matrix and fibronectin, but not to type IV collagen. TPA-enhanced adhesion can be reduced by lipoxygenase inhibitors but not by cyclooxygenase inhibitors and in addition, stimulated adhesion can be blocked by pretreatment of tumor cells with specific polyclonal or monoclonal antibodies which react against IRGpIIb/IIIa. 12(S)-HETE-enhanced adhesion can also be inhibited by these same antibodies. In contrast, a lipoxygenase product of linoleic acid, 13(S)-hydroxyoctadecadienoic acid, inhibited TPA and 12(S)-HETE-enhanced tumor cell adhesion to endothelial cells, subendothelial matrix, and fibronectin. These results suggest that (a) IRGpIIb/IIIa is a multifunctional receptor which mediates tumor cell adhesion to a variety of biological substrata, (b) TPA enhances surface expression and/or activation of this receptor possibly via a lipoxygenase metabolite of arachidonic acid, and (c) these effects are opposed by a lipoxygenase metabolite of linoleic acid.
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PMID:Bidirectional control of membrane expression and/or activation of the tumor cell IRGpIIb/IIIa receptor and tumor cell adhesion by lipoxygenase products of arachidonic acid and linoleic acid. 249 4


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