Biomedical subjects

S Filsinger

Publications and source records attributed to S Filsinger.

10 recordsLinked to original sources

PubMed1998

Synovial fibroblasts as target cells for staphylococcal enterotoxin-induced T-cell cytotoxicity.

Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown aetiology. Recently, superantigens have been implied in the pathogenesis of RA. Superantigens activate a large fraction of T cells leading to the production of cytokines and proliferation. In addition, superantigens direct cellular cytotoxicity towards major histocompatibility complex (MHC) class II-expressing cells. There is now increasing evidence that cytotoxic T cells may be involved in the pathogenesis of RA. In the inflamed synovia class II-positive synovial fibroblasts (SFC) are found. In the present study it was tested whether MHC class II-positive SFC serve as target cells for superantigen-induced cellular cytotoxicity. SFC were stimulated with interferon-gamma to express class II antigens, then they were cultivated in the presence of CD4-positive T cells with or without staphylococcal enterotoxins (SE). Cytotoxicity of T cells was measured as release of lactate dehydrogenase from SFC. Specific cytotoxicity was only found in the presence of class II-positive SFC depending on the dose of SE. Maximum lysis was seen after 20 hr. T-cell cytotoxicity was inhibited by antibodies to MHC class II antigens. The data suggest that class II-positive SFC not only function as accessory cells for SE-mediated T-cell proliferation and interleukin-2 production but may also be the targets of superantigen-mediated cellular cytotoxicity.

Antibodies, Monoclonal↗

PubMed1996

Interaction of transforming growth factor beta 1 with human glomerular epithelial cells in culture: opposite effects on synthesis of matrix proteins and on urokinase plasminogen activator.

The effect of transforming growth factor-beta (TGF-beta) was analyzed on the synthesis of fibronectin, collagen type IV, and urokinase plasminogen activator in human glomerular epithelial cells in culture. An increase in the abundance of specific mRNA was found for collagen type IV and fibronectin. Fibronectin protein synthesis was also increased in TGF-beta treated cells; most of the de novo synthesized fibronectin was found as an unsoluble protein associated with extracellular matrix. In the same cells the amount of plasminogen activator mRNA was found leading also to a decreased surface expression of urokinase plasminogen activator. The data support the concept that by upregulating matrix protein synthesis and downregulating the plasminogen activator system, TGF-beta favors the development of sclerosis.

Cells, Cultured↗

PubMed1996

Expression of the 14 kDa galactose-binding protein, galectin-1, on human tubular epithelial cells.

By reverse phase PCR and Northern blotting, RNA of the 14 kDa galactose-binding protein (galectin-1) could be identified in primary cultures of human tubular epithelial cells. To assess protein synthesis and the possible function of galectin-1 on TEC, the cellular proteins were biosyntheticically labeled with [34S]-methionine and absorbed to immobilized laminin. Multiple radiolabeled proteins were eluted, a strong band in the area of 14 kDa was seen, coinciding with the galectin-1 band as identified by Western blotting. Surface expression of galectin-1 was seen by cytofluorometry with two different polyclonal antibodies to galectin-1. These data are in line with the finding that tubular epithelial cells adhere to laminin, partly in a Ca(2+)-independent manner.

Antigens, Surface↗

PubMed1995

Comparative phenotypic analysis of lymph node cells in mice after infection or vaccination with normal or ultraviolet-attenuated cercariae of Schistosoma japonicum or S. mansoni.

Mice were infected with 200 untreated or vaccinated with 500 ultraviolet-attenuated cercariae of either Schistosoma japonicum or S. mansoni. For three weeks, cell numbers in axillary and mediastinal lymphnodes were counted and cell populations typed by cytofluorometry. In the axillary lymphnodes, numbers of B-cells and CD3+CD4+ T-cells but not CD3+CD8+ T-cells increased. Following vaccination with either species, parasite migration was apparently delayed in the skin and interrupted at the lungs, the lymphnodes gained weight, and cell numbers of axillary lymph nodes increased more than after infection. In mediastinal lymphnodes, only immunization with S. japonicum but not S. mansoni cercariae led to an increase of CD3+CD4+ T-cells. Following infection, both schistosome species induced higher CD3+CD4+, but not CD3+CD8+ T-cells in mediastinal nodes, and the peak was earlier with S. japonicum (about seven days after infection) than with S. mansoni (about 10 days). In analogy to T-cell observations by others using a gamma-attenuated cercarial vaccine in S. mansoni, the present results suggest that CD3+CD4+ cells also play a role in the ultraviolet-attenuated vaccine against S. japonicum.

Animals↗

PubMed1995

Synovial fibroblasts as accessory cells for staphylococcal enterotoxin-mediated T-cell activation.

Rheumatoid arthritis (RA) is thought to be the result of T-cell-mediated autoimmune phenomena. So far, a critical autoantigen has not been identified. Recently, superantigens have been implied in the pathogenesis of RA. In the present study it was tested whether major histocompatibility complex (MHC) class II-positive synovial fibroblast cells (SFC) function as superantigen-presenting cells. SFC were stimulated with interferon-gamma (IFN-gamma) to express class II antigens; then they were cultivated in the presence of T cells with or without staphylococcal enterotoxins (SE). T-cell activation was measured as proliferation and interleukin-2 (IL-2) production. Depending on the dose and type of SE, activation of T-cell clones and also of peripheral T cells was seen. T-cell activation was inhibited by antibodies to MHC class II antigens and also by antibodies to intracellular adhesion molecule type-1 (ICAM-1). The data suggest that class II-positive SFC have the capacity to serve as accessory cells for superantigen-mediated T-cell activation. Thus SFC may participate in the propagation of a T-cell dependent immune response.

Antigen-Presenting Cells↗

PubMed1993

Interaction of the terminal complement components C5b-9 with synovial fibroblasts: binding to the membrane surface leads to increased levels in collagenase-specific mRNA.

The late complement components, apart from their lytic function, are known to trigger the release of various proinflammatory substances from different types of nucleated cells. In the present study, the interaction of C5b-9 with synovial fibroblast cells (SFC) was examined. It was found that incubation of SFC with activated complement components resulted in binding of C5b-9 to the cell membrane; subsequently an increase in abundance of collagenase-specific mRNA was seen, as assessed by Northern blotting. When C8-deficient serum was used as source of complement neither binding of C5b-9 nor an increase in collagenase-specific mRNA could be detected. These findings suggest that C5b-9, which might be generated during rheumatoid inflammation, may contribute to chronic joint destruction by triggering collagenolytic activity.

Arthritis, Rheumatoid↗

PubMed1988

The C8-binding protein of human erythrocytes: interaction with the components of the complement-attack phase.

C8-binding protein is an intrinsic membrane protein of the human erythrocyte. It inhibits the complement (C5b-9)-mediated lysis in a species-restricting manner. In the present study we incorporated C8bp, isolated from human erythrocytes, into sheep erythrocytes (SRBC). SRBC, normally sensitive to lysis by human C5b-9, became insensitive to lysis. Furthermore, we found that C8bp is incorporated into the membrane-attack complex C5b-9, most probably by interacting with C8, since C8bp has an affinity for C8, particularly for the C8 alpha-gamma-subunit. Antibodies to C8bp react with the C8 alpha-subunits and with C9, pointing to the possibility of a partial homology between these proteins.

Animals↗

PubMedDate not supplied

C8 binding protein bears I antigenic determinants.

C8 binding protein (C8bp) is an integral membrane glycoprotein of peripheral blood cells, which inhibits the C5b-9-mediated lysis in a homologous system. In the present study, we analyzed the carbohydrate portion of the C8bp. We found that C8bp is associated with I antigenic determinant, a sugar sequence found on human erythrocytes of adults. To assess whether or not the sugar residues are essential for the C8bp function, I determinant was cleaved off from the isolated C8bp by endo-beta-galactosidase (E.C. 3.2.2.103) that hydrolyses internal beta-galactosidic-linked-N-acetyllactosamine residues. Enzyme treatment removed I-antigen, the inhibitory function of C8bp, however, was not affected. When intact erythrocytes were treated with endo-beta-galactosidase, I-antigen was lost and the lytic insusceptibility of human erythrocytes to homologous C5b-9 could not be abolished. Thus, I-antigen is associated with the C8bp, but its presence is not required for the homologous species restriction.

Blood Proteins↗

PubMedDate not supplied

Tubular epithelial cells as accessory cells for superantigen-induced T cell activation.

In various inflammatory kidney diseases, tubular epithelial cells (TEC) express major histocompatibility complex class II antigens. To assess whether they might have the capacity to directly activate T cells, human TEC in culture were treated with gamma interferon to induce class II expression. TEC were then cocultivated with staphylococcus enterotoxin and cloned T cells or highly purified peripheral T cells. After 1-2 days, release of interleukin 2 and of gamma interferon was seen; after 3-5 days T cell proliferation occurred. The proliferation could be inhibited by antibodies to class II antigens or by antibodies to ICAM-1; the latter is also expressed on TEC in inflammatory processes and on TEC in culture as well. In conclusion, human TEC might function as accessory cells for T cell activation and might support T cell dependent immune response.

Antibodies↗

PubMedDate not supplied

Fibronectin modulates interleukin 6 and fibronectin synthesis of human glomerular mesangial cells in culture.

In this paper we report that fibronectin (FN) and its proteolytic 120-kD fragment regulate synthesis and secretion of interleukin 6 (IL-6) and of FN by human glomerular mesangial cells. While intact FN and a fragment derived from the heparin-binding domain had no effect on IL-6 secretion, the 120-kD FN fragment containing the cell attachment site stimulated secretion by 40-fold. The same FN fragment reduced FN secretion and the steady state mRNA level by 80%. The intact FN showed only a weak inhibitory effect (+/- 30%); the 30-kD fragment containing the heparin-binding domain had no effect. The effects of the 120-kD FN were inhibited by the peptide RGDS, implying participation of the cell attachment site in signal transduction. An antibody to the alpha-chain of VLA-3 mimicked the effect of the 120-kD FN, whereas an antibody to the alpha-chain of VLA-5 was partly inhibitory. Taken together, the data suggest that FN by interacting with its receptors differentially regulates the protein synthesis of glomerular mesangial cells, promoting IL-6 secretion and inhibiting FN synthesis.

Antibodies↗