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At least 109 records · Page 6Linked to original sources
PubMed1989

Matrix-associated heparan sulfate proteoglycan: core protein-specific monoclonal antibodies decorate the pericellular matrix of connective tissue cells and the stromal side of basement membranes.

Cultured human lung fibroblasts produce a large, nonhydrophobic heparan sulfate proteoglycan that accumulates in the extracellular matrix of the monolayer (Heremans, A., J. J. Cassiman, H. Van den Berghe, and G. David. 1988. J. Biol. Chem. 263: 4731-4739). A panel of four monoclonal antibodies, specific for four distinct epitopes on the 400-kD core protein of this extracellular matrix heparan sulfate proteoglycan, detects similar proteoglycans in human epithelial cell cultures. Immunohistochemistry of human tissues with the monoclonal antibodies reveals that these proteoglycans are concentrated at cell-matrix interfaces. Immunogold labeling of ultracryosections of human skin indicates that the proteoglycan epitopes are nonhomogeneously distributed over the width of the basement membrane. Immunochemical investigations and amino acid sequence analysis indicate that the proteoglycan from the fibroblast matrix shares several structural features with the large, low density heparan sulfate proteoglycan isolated from the Engelbreth-Holm-Swarm sarcoma. Thus, both epithelial cell sheets and individual mesenchymal cells accumulate a large heparan sulfate proteoglycan(s) at the interface with the interstitial matrix, where the proteoglycan may adopt a specific topological orientation with respect to this matrix.

Amino Acid Sequence↗
PubMed1984

[Effect of the secretion products of mononuclear phagocytes on the proliferative activity of connective tissue cells].

3H-thymidine uptake was used to study the effect of the media conditioned by murine peritoneal macrophages and human peripheral blood monocytes on proliferative activity of 3T3 fibroblasts, smooth muscles of the umbilical vein and bone marrow fibroblasts. Secretory products of murine macrophages and human blood monocytes inhibited the proliferation of all 3 types of target cells. Latex phagocytosis by macrophages led to the increase in the inhibitory activity of the media conditioned by macrophages, whereas upon latex phagocytosis by monocytes the inhibitory action of the conditioned media was unchanged. Addition of rodexman to monocyte cultures did not produce any effect on the inhibitory action of the conditioned media. Activation of monocytes by lipopolysaccharide resulted in the diminution of the inhibitory action of the monocyte-conditioned media only with respect to smooth muscle cells. Lipopolysaccharide did not affect the action of the media conditioned with macrophages.

Animals↗
PubMed1992

Compatibility of intraocular lenses with blood and connective tissue cells measured by cellular deposition and inflammatory response in vitro.

Injection molded poly(methyl methacrylate) (IM-PMMA), lathe-cut PMMA (LC-PMMA), heparin surface modified PMMA (HSM-PMMA), silicone, and polyhydroxyethyl methacrylate (polyHEMA) intraocular lenses (IOLs) were incubated with platelets, granulocytes, mouse macrophage-like RAW 264.7 cells and mouse fibrosarcoma L929 cells to examine their compatibility. The number of cells attached to the IOL was counted after the central IOL area (0.04 mm2) was photographed with an inverted light microscope. Cell morphology was examined by scanning electron microscopy (SEM). More platelets and granulocytes were attached to the IM-PMMA and silicone IOLs than to the HSM-PMMA and polyHEMA IOLs (P less than .05). RAW 264.7 and L929 cells grew on PMMA-based and silicone IOLs, whereas HSM-PMMA and polyHEMA IOLs did not support an abundant growth of these cells. Granulocytes were incubated with the IOLs in the presence of Luminol and the generation of chemiluminescence was measured. Poly(methyl methacrylate)-based IOLs caused granulocytes to release significant amounts of oxygen radicals, while the polyHEMA IOL was almost inactive in stimulating granulocytes. Silicone and HSM-PMMA IOLs showed an intermediate level of stimulating activity. The light intensity reached a peak within 14 minutes with the IM-PMMA IOL, and in about 18 minutes with the other IOLs. Our results suggest that IOL hydrophilicity prevents attachment of cells and that a hydrophilic, soft surface can discourage granulocyte stimulation.

Animals↗
PubMed1995

Interactions of connective tissue cells with the extracellular matrix.

Interactions between cells and extracellular matrix components have been shown to be crucial for the regulation of tissue differentiation and function in a range of organisms. Recent work has defined several families of receptors by their domain structure, and the peptide sequence motifs in the ligands which they recognize have been elucidated. Thus, the integrin fibronectin receptor has been shown to recognize "RGD" and other sequences within matrix and plasma proteins. Disruption of these integrin-ligand interactions by gene inactivation via homologous recombination of receptor or ligand, and by use of RGD inhibitors or antibodies, modifies embryonic development and cellular function. Recent evidence from several receptor systems has also demonstrated that they can partake in signal transduction, in addition to adhesive events, leading to the definition of further functional activities. The range of receptors and their ligands involved in matrix interactions and data on their role in a variety of cellular systems are summarized. The therapeutic implications of a fundamental approach to cellular adhesion processes will be highlighted by considering the role of the alpha v beta 3 integrin receptor in osteoclastic bone resorption.

Amino Acid Sequence↗
PubMed1990

Interaction of immune and connective tissue cells: I. The effect of lymphokines and monokines on fibroblast growth.

In order to determine if mononuclear cells may be secreting factors capable of modulating fibroblast growth, the in vitro proliferative response of fibroblasts to cytokines known to be secreted by mononuclear cells was measured, using both growth arrested and proliferating cells. Of the cytokines tested, which included interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-4 (IL-4), interleukin-6 (IL-6), interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), transforming growth factor-alpha (TGF-alpha), transforming growth factor-beta (TGF-beta), platelet derived growth factor (PDGF), and tumor necrosis factor-alpha (TNF-alpha), only TNF-alpha and PDGF had demonstrable growth factor activity. Neither IL-1 alpha nor beta showed any true growth factor activity but were able to enhance the replication of already proliferating cells. No inhibition of proliferation was noted by any of the cytokines with the exception of TNF-alpha and TGF-beta. TNF-alpha in doses greater than 500 ng/ml caused fibroblast death, probably by a prostaglandin related mechanism as fibroblasts remained viable, although non proliferative, when assayed in the presence of indomethacin, a known inhibitor of prostaglandin E2 (PGE2) synthesis. TGF-beta was inhibitory to proliferation at doses greater than 100 ng/ml, while fibroblasts remained viable. This effect was not influenced by indomethacin and hence is unlikely to be PGE2 related.

Cell Division↗
PubMed1978

The effects of diphosphonates on the growth and glycolysis of connective-tissue cells in culture.

1. The effects of two diphosphonates (compounds containing a P-C-P bond), disodium dichloromethanediphosphonate and disodium 1-hydroxyethane-1,1-diphosphonate, on the metabolism of cultured rat calvaria cells, rabbit ear cartilage cells and rat skin fibroblasts were investigated. 2. The diphosphonates had no effect on the growth of cartilage cells and on the exponential growth of the calvaria cells and the fibroblasts. However, dichloromethanediphosphonate stopped the growth of the calvaria cells and the fibroblasts after the beginning of confluence, whereas the untreated cells were still growing to a certain extent. This inhibition was dose-dependent. After the drug was withdrawn, the cells recovered slowly. 1-Hydroxyethane-1,1-diphosphonate had no detectable effect on the growth of any of the cell types studied. Both diphosphonates decreased the cloning efficiency of calvaria cells and fibroblasts. 3. The K+ content of cartilage, calvaria and skin cells was diminished only by the highest (0.25 mM) concentration of dichloromethanediphosphonate. 4. Radioactive dichloromethanediphosphonate and 1-hydroxyethane-1,1-diphosphonate were taken up linearly with time for at least 48 h by calvaria cells and fibroblasts. The diphosphonate concentration in the cells depended on its concentration in the medium. 5. Both diphosphonates, in a dose-dependent fashion, markedly inhibited glycolysis, dichloromethanediphosphonate being more effective than 1-hydroxyethane-1,1-diphosphonate, at drug doses that had no effect on cell growth or cellular K+ content. Calvaria cells were much more sensitive than cartilage cells. When cartilage cells were cultured in an N2 atmosphere, these effects on glucose and lactate metabolism disappeared. 6. As increased acid production appears to be associated with resorption of bone, this decrease in lactate may explain why diphosphonates are effective inhibitors of bone resorption in vivo.

Animals↗
PubMed1988

Effect of lymphotoxin and tumor necrosis factor on endothelial and connective tissue cell growth and function.

In an approach to understand the immune basis of human vascular and fibrotic disorders, the effects of recombinant human tumor necrosis factor alpha (rTNF) and lymphotoxin (rLT) on the in vitro growth and function of vascular and connective tissue cells were studied. Both rTNF and rLT stimulated fibroblast growth and protein, fibronectin, and collagen synthesis in dose-dependent fashion. In contrast, endothelial cell (EC) growth was inhibited by both cytokines; true EC cytotoxicity was seen at high concentrations (greater than or equal to 500 mu/ml). Addition of recombinant interferon-gamma markedly enhanced EC cytotoxicity while the growth factor beta-transforming growth factor reversed EC growth inhibition. Both rTNF and rLT stimulated factor VIII-Ag synthesis by EC. These contrasting effects of rTNF and rLT on fibroblast and endothelial cell growth and function in vitro are intriguing because they are the same contrasting effects observed in vivo in connective tissue and vascular disorders, raising the possibility of a role for these cytokines in these disorders. Study of the in vitro and in vivo mechanisms of these diverse effects may contribute to the understanding of certain human disorders characterized by endothelial injury and fibroblast activation leading to fibrosis.

Animals↗
PubMed1982

Ultrastructure of human osteosarcoma. Malignant transformation of a multipotential connective tissue cell.

Ten cases of osteosarcoma were studied by electron microscopy. The tumors consisted of six cell types: fibroblastic, myofibroblastic, chondroblastic, osteoblastic, unclassified and histiocytic cells. Disturbed structure of dilated endoplasmic reticulum was a common feature. The neoplastic character of myofibroblastic and histiocytic cells is controversial. Myofibroblastic differentiation was most abundant in parosteal osteosarcoma and in fibrosarcomatous intraosseal osteosarcoma. The malignant cells sometimes formed giant cells and many aggregates of these cells were seen. Osteoclasts and other reactive cells were encountered and this may indicate host reaction against the tumor cells. Formation of collagenous and cartilaginous ground substance was poor, and the capacity of collagen to mineralize was decreased. It is concluded that osteosarcoma is the malignancy of a multipotential connective tissue cell which forms callus in normal osteogenesis.

Adolescent↗
PubMed1977

Cell surface-associated structural proteins in connective tissue cells.

Collagen and/or procollagen was demonstrated on the surface of monolayers of fibroblasts from normal rat kidney by indirect immunofluorescence with affinity-purified antibodies to collagen. The protein was arrayed in a reticular fashion on the cell surface and, in cells attached to a substratum, was severely restricted in its ability to undergo antibody-induced translational movement in the plane of the membrane. A similar pattern was observed for fibronectin (LETS protein, fibroblast surface antigen). These macromolecules were lost when fibroblasts were dissociated and examined in suspension cultures and were not regained until after the cells were replated. On the basis of the morphological findings, and in view of the likelihood of an interaction between fibronectin and collagen, we propose that these that these proteins form a meshwork on the cell surface. This external protein meshwork may mediate a number of important cellular functions, including attachment to a substratum and other interactions with the extracellular matrix.

Cell Line↗
PubMed1993

Pluripotent and developmentally restricted neural-crest-derived cells in posterior visceral arches.

The early migratory cells of the posterior rhombencephalic neural crest consist of a heterogeneous population of pluripotent and developmentally restricted neural crest cells (Ito and Sieber-Blum, Dev. Biol. 148, 95-106, 1991). To determine if changes in developmental capacities occur during migration, the developmental potentials of posterior visceral arch mesenchymal cells were investigated by in vitro clonal analysis. Most of these cells consisted of the post-migratory cells of the posterior rhombencephalic neural crest. Four morphologically distinct types of clones were observed, and the cells within these clones expressed characteristic phenotypes as shown by their binding of antibodies against cell type-specific markers: (1) "DP" clones consisted of densely packed polygonal cells, with flattened large cells located predominantly at the periphery of these clones. Immunocytochemical analyses showed that DP clones contained smooth muscle cells, connective tissue cells, chondrocytes, and serotonin (5-HT)-positive neurons, and over 90% of the cells per clone were HNK-1 positive. This suggests that DP clone-forming cells are pluripotent neural-crest-derived cells with the capacity to develop into ectomesenchymal derivatives and serotonergic neurons. (2) "DS" clones consisted of densely packed spindle-shaped cells. These clones included smooth muscle cells, connective tissue cells, and chondrocytes. By contrast, neuronal phenotypes were not present. An average of 0.4% of the cells per clone were HNK-1 positive. DS clones appear to be formed by neural-crest-derived cells that are partially restricted, expressing ectomesenchymal phenotypes only. (3) "DF" clones consisted of densely packed small cells and flattened large cells. Although no HNK-1-positive cells were found in DF clones, these clones contained connective tissue cells and/or smooth muscle cells. DF clones appear to be derived from bipotent cells with the ability to differentiate into connective tissue cells and smooth muscle cells, or cells committed to the connective tissue cell lineage. (4) "LF" clones consisted of loosely arranged, flattened large cells. These clones did not contain HNK-1-positive cells. The clones consisted entirely of smooth muscle cells. Therefore, LF clones are most likely formed by precursors that are committed to the smooth muscle cell lineage. These results indicate the presence of pluripotent neural-crest-derived cells, cells with a restricted developmental potential, and apparently committed cells in the posterior visceral arch. Pluripotent cells can generate up to four neuronal and non-neuronal phenotypes. Other cells are restricted to ectomesenchymal cell types, and the proportion of these cells in the posterior visceral arch changes with progressing embryonic development.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2000

Schistosoma mansoni egg-induced hepatic granulomas in mice deficient for the interferon-gamma receptor have altered populations of macrophages, lymphocytes and connective tissue cells.

Systemic production and mobilization of inflammatory cells and formation of hepatic periovular granulomas were studied in Schistosoma mansoni-infected mice with deficient interferon gamma (IFN-gamma) receptor (IFN-gammaR(o/o)). The impaired IFN-gamma signaling did not cause a significant modification of the overall kinetics of inflammatory cells, but mutant mice developed smaller hepatic periovular granulomas with a two-fold reduction in all the cell lineages. In granulomas of normal mice, the fully differentiated macrophages were progressively predominant, whilst in IFN-gammaR(o/o) mice, the granulomas contained a higher percentage of immature and proliferating monocytes. Granulomas of IFN-gammaR(o/o) mice had an enhanced and accelerated fibrotic reaction, corresponding to an increased content of proliferative and activated connective tissue cells. Simultaneously, their granulomas had an increased ratio of T over B cells, with an increase in CD8(+) and a reduction in CD4(+) T cells. The functional IFN-gamma receptor was not required for initial recruitment of monocytes and lymphocytes into granulomas, but it was necessary for the maturation of macrophages, upregulation of major histocompatibility class 2 (MHC-II) expression and consequent stimulation of lymphocyte subpopulations depending upon the MHC-II-mediated antigen presentation.

Animals↗