Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.4.24.3 (collagenase)
18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary cultures of adherent rheumatoid synovial cells contain variable proportions of fibroblasts, macrophages, and dendritic cells, as judged by morphological appearance. Comparative studies using various enzymic and histochemical staining procedures showed the dendritic cells to lack many of the characteristic features of macrophages, e.g. the failure to express HLA-DR (Ia) antigen. The dendritic cells and fibroblasts had several similarities, but differed to some extent in their nonspecific esterase activity, phagocytic and proliferative potential. As the proportions of dendritic cells and fibroblasts varied in relation to specific culture conditions, we examined the possibility that these morphologies might represent different functional states rather than distinct cellular origins. Using subcultured synovial fibroblasts with a uniform bipolar appearance, we have shown that exposure to interleukin-1 or mast cell products resulted in a transformation to dendritic morphology. This change in cell shape was prevented by the presence of indomethacin, but was subsequently achieved by the addition of exogenous PGE2. Thus it appears that the latter is the factor that modulates the morphological change of fibroblastic to dendritic cells. This study has also demonstrated the complete and reversible interchange of fibroblast/dendritic morphology, thereby confirming that these different shapes are manifest by the same cell. The changes in phenotypic expression associated with the dendritic appearance include increased production of collagenase, prostaglandin E, and nonspecific esterase, as well as an apparent inability to exhibit phagocytosis and to proliferate in culture. We conclude from our in vitro studies that the phenotypic behaviour of the synovial fibroblast (or synoviocyte) is very variable and dependent to a large extent upon local stimuli, but the identity and hierarchy of such stimulating and suppressive factors in relation to cellular interactions requires further study.
...
PMID:Comparative studies of adherent rheumatoid synovial cells in primary culture: characterisation of the dendritic (stellate) cell. 349 52

A subpopulation of human synovial cells develop a stellate morphology during in vitro culture. These cells, called stellate cells or dendritic cells, appear capable of collagenase production. In other tissues, particularly mouse spleen and human peripheral blood, cells with a similar shape express immune region associated (Ia) antigens, stimulate a primary mixed leukocyte reaction, and present antigen to lymphocytes. To characterize synovial dendritic cells, we observed changes in their morphology by time-lapse videomicroscopy. Parallel cultures of cells from the same specimens were observed periodically for HLA-DR surface antigens by immunofluorescence microscopy. During culture, synovial dendritic cells gradually lost their distinct morphologic appearance and became indistinguishable from fibroblasts. Moreover, fibroblasts occasionally assumed a dendritic morphology. When cells were examined at 24-48 h or later, we could not detect HLA-DR antigens on synovial dendritic cells, defined as cells with 4 or more stellate, branching projections. Cells with only 1-3 projections often had HLA-DR antigens. Because human synovial dendritic cells may lose their characteristic morphology upon culture and because they appear to lack Ia antigens in the unstimulated state, we suggest that synovial dendritic cells may be closely related to fibroblasts.
...
PMID:Human synovial dendritic cells. Direct observation of transition to fibroblasts. 386 55

Human endothelial cells were obtained by collagenase digestion of the umbilical vein wall, explanted into tissue culture, and grown as monolayers of cells. Endothelial cells extracted from these monolayers were specifically lysed by anti-HLA-DR alloantisera. Moreover, the stimulating capacity of these endothelial cells toward allogeneic peripheral blood mononuclear lymphocytes was specifically and significantly inhibited by the presence of relevant anti-HLA-DR antisera. Endothelial cells that expressed HLA-DR determinants were also capable of substituting for macrophages in the lymphoproliferative response of purified T cells to soluble protein antigens. Moreover, in concordance with the results previously reported in which macrophages were employed, the endothelial cell donor should share HLA-DR determinants with the T cell donor for an optimal response to occur.
...
PMID:Antigen-presenting properties of human vascular endothelial cells. 615 67

Surface markers of human gingival fibroblasts in vitro were investigated using monoclonal and heterologous antisera against a range of cell surface antigens, together with rosetting techniques to characterize surface receptors for IgG and C3. WI-38 fibroblasts and human peripheral blood monocytes were used as control cells. Human gingival fibroblasts exhibited complement receptors and beta2-microglobulin, as did WI-38 cells. Ten per cent of the human gingival fibroblasts were positive for HLA-DR antigens and additionally exhibited a granulocyte antigen not apparent on WI-38 cells. Monolayers of the gingival fibroblasts were further exposed for short periods to varying concentrations of enzymes (trypsin, collagenase and neuraminidase), bacterial extracts (lipopolysaccharide and lipoteichoic acid) and crude supra- and subgingival plaque sonicates. Surface-marker analysis was then carried out. The most noticeable effects were obtained with Vibrio cholerae neuraminidase which enhanced C3 receptor and surface antigen expression, and supragingival plaque sonicate which depressed the expression of HLA-DR and granulocyte antigens while not affecting beta2-microglobulin expression. Trypsin reduced antigen expression to a degree, but its effects were mainly on cell adherence.
...
PMID:Surface markers of human gingival fibroblasts in vitro. Characterization and modulation by enzymes and bacterial products. 633 Mar 32

Rheumatoid Arthritis is a chronic, usually progressive inflammatory disorder of joints in which the immune system plays a central role in the pathogenesis. In its classic form, the synovial tissues from severely affected joints are densely infiltrated with HLA-DR bearing T-lymphocytes (primarily OKT4+/Leu3+ subset) and macrophage-like cells. Moreover, these tissues, as demonstrated by ex vivo culture, spontaneously produce high levels of a multitude of inflammatory mediators, such as collagenase, PGE2, interleukin 1 and fibroblast activating factors, indicating that the cells infiltrating the synovium are "activated". The action of these various inflammatory mediators on different target substances or cells (collagen, fibroblasts, chondrocytes, osteoclasts, etc.) most likely produce the characteristic pattern of joint pathology. Recent data indicate that this classic form of synovitis tends to be associated with peripheral anergy and other qualitative and quantitative abnormalities in the peripheral blood mononuclear cells. Repeated leukapheresis can induce substantial, although transient, clinical improvement in patients with these classic features, probably as a consequence of disrupting T-lymphocyte traffic. Rheumatoid synovitis, however, is highly heterogeneous, but can be categorized into subsets. For example, a subset of patients with highly active clinical rheumatoid arthritis exists which do not exhibit the classic features of disease. Synovial tissues from this patient subset are sparsely infiltrated by T-lymphocytes but contain mainly macrophages and fibroblasts, as well as prominent lining layer fibrin deposition.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Leukapheresis and pathogenetic mechanisms in rheumatoid arthritis. 633 86

The presence and the ontogeny of class I and class II major histocompatibility (MHC) antigens were investigated on human trophoblast cells in single cell suspensions of collagenase dispersed placentae during the first trimester of pregnancy by using a highly sensitive radioautographic approach. Cells were treated with monoclonal anti-HLA-A,B,C or anti-HLA-DR (or anti-human Ia) antibodies followed by 125I-labeled protein A, normal mouse serum, or medium alone used as negative controls, and monoclonal antibodies against trophoblast specific antigenic markers (anti-Trop 2, NDOG-1, and NDOG-2) used as positive controls for specificity of trophoblast labeling. Tissue controls were provided by Ficoll-paque-separated adult human peripheral blood lymphocytes (PBL), and placental lymphocytes were used as additional internal controls. Results revealed variable but specific labeling of cytotrophoblast cells for class I but not class II MHC antigens at all gestational stages during the first trimester. The incidence of HLA-A,B,C antigen-bearing cytotrophoblast cells in early gestational (5 to 8 wk) placentae was high (75 to 91%) in the minority, but was low to medium (35 to 66%) in placentae at later gestational intervals (9 to 12 wk). The initial antigen density on the labeled cytotrophoblast cells as reflected by the median silver grain counts per unit area was approximately 75% of that noted on adult PBL or placental lymphocytes at 5 to 7 wk. The density then dropped to 50% of the initial level by the eighth week of gestation with no further change up to 12 wk. Syncytiotrophoblast cells revealed no appreciable labeling for either antigen class. This could not be explained by antigen stripping due to the collagenase dispersion procedure; specific labeling was not detectable on the syncytiotrophoblast cell layer in situ in histologic sections after intact chorionic villi had been directly exposed to 125I-labeled monoclonal anti-class I antibody. These results are qualitatively similar to our findings in the mouse in revealing the presence of class I MHC antigens on a major population of trophoblast cells.
...
PMID:Ontogeny of the MHC antigens on human trophoblast cells during the first trimester of pregnancy. 641 63

The reactivity of rabbit anti-HLA-DR antigen antibodies with cells in normal and rheumatoid synovial tissue was investigated by indirect immunofluorescence on frozen sections of tissue. The antibodies reacted with a significant proportion of the synovial lining cells of both normal and rheumatoid synovial tissue, with endothelial cells, and with a number of, most probably, migratory cells. After dispersion of cells from rheumatoid synovial tissue by digestion with collagenase and DNase, adherent cells of both a macrophage-like and a dendritic appearance reacted with the anti-HLA-DR antigen antibodies. The adherent cells were also found to be potent stimulators in the allogeneic MLR. In addition, it was found that a high percentage of T lymphocytes from both peripheral blood and synovial tissue of rheumatoid patients bound anti-HLA-DR antibodies. The present data suggest a role for synovial lining cells in HLA-D-locus-dependent events of importance in the pathogenesis of rheumatoid arthritis and other joint diseases and point to the need for further investigations on T lymphocytes derived from the site of inflammation in the study of rheumatoid arthritis.
...
PMID:Appearance of anti-HLA-DR-reactive cells in normal and rheumatoid synovial tissue. 645 80

Monolayer cultures of renal tubular (hKEC) cells were established. These cells formed empty spheroids after 2-3 weeks of culture in a collagen gel matrix. A subcellular polarity from the apex to basement was induced in these "spheroidal" hKEC cells. The weak expression of laminin at the outer surface was evident on spheroidal but not on monolayered hKEC cells. The regulation of HLA-ABC, DR, and intercellular adhesion molecule-1 (ICAM-1) antigens on hKEC cells in the gel matrix was investigated utilizing digestion of gel matrix by collagenase. Enzymatic digestion of the collagen gel did not significantly affect the surface expression of HLA-ABC and ICAM-1, but reduced HLA-DR expression as shown by flow cytometry. The MHC and ICAM-1 molecules on both spheroid-forming and monolayered hKEC cells were upregulated by adding a supernatant of mixed lymphocyte reaction (MLR) and recombinant human interferon (IFN)-gamma. HLA-DR antigen expression was inconsistently induced on the hKEC cells cultured in collagen gel without MLR supernatant or IFN-gamma. In contrast, no HLA-DR expression was found on monolayered hKEC cells in the absence of MLR supernatant or IFN-gamma. Spheroid-forming hKEC cells, when dispersed by enzymatic digestion, were more susceptible to cytolysis by lymphokine-activated killer (LAK) cells than were the enzymatically dispersed, monolayered cells in the 51Cr-release assay. The LAK cells were seen to migrate into the collagen gel and kill the hKEC cells. Thus, LAK cells may function to favor the acceleration of graft rejection.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Susceptibility of renal tubular cells to lymphokine-activated killer (LAK) cells: application of culture system using a collagen gel matrix. 809 21

The matrix metalloproteinases (MMPs) collagenase, gelatinase A (72 kDa gelatinase), stromelysin, and their specific inhibitor TIMP-1 (tissue inhibitor of metalloproteinases), were immunolocalized using specific polyclonal antisera in gingival tissues from 21 patients with chronic inflammatory periodontal disease. Monoclonal antibodies against macrophages (Leu-M5), B cells (Leu-14), helper T cells (OKT4), suppressor T cells (OKT8) and the HLA-DR epitope were also used to identify leukocyte subsets. MMPs were observed in connective tissues at sites that histologically showed signs of remodelling. The number and distribution of positive cells varied widely, however, not only between individual biopsy specimens, but also within the same specimen. The same was true for the composition and distribution of the inflammatory cell infiltrate. Moreover, although there was a positive correlation between the number of MMP-producing cells and the severity of inflammation in some specimens, for others with comparable leukocyte subset scoring the number was reduced and sometimes absent altogether. Cells secreting MMPs were fibroblasts, macrophages and epithelial cells. It was not possible to determine unequivocally whether a MMP-positive cell within the connective tissue was a fibroblast or a macrophage, since the antisera recognise both fibroblast and macrophage MMPs and the different fixation requirements for MMPs (4% paraformaldehyde) and Leu-M5 (acetone) precluded co-localization on the same section. TIMP-1 was immunolocalized within connective tissue cells at sites of tissue remodelling. Our results support the hypothesis that tissue-derived MMPs may be involved in tissue remodelling in periodontal disease and conclusively demonstrate that epithelial cells may be involved as well as connective tissue cells.
...
PMID:Immunolocalization of matrix metalloproteinases and TIMP-1 (tissue inhibitor of metalloproteinases) in human gingival tissues from periodontitis patients. 815

We recently described mutual antagonism between IFN-gamma and TNF-alpha on human fibroblast-like synoviocytes (FLS). TNF-alpha inhibits IFN-gamma-induced HLA-DR expression and IFN-gamma blocks TNF-alpha-dependent synoviocyte proliferation, collagenase production, and GM-CSF secretion. To study the mechanism of antagonism we have analyzed the effect these factors on the expression of cytokine surface receptors. 125I-Labeled cytokine binding was measured on cultured FLS and the results were analyzed by Scatchard plots. Unstimulated synoviocytes expressed 9300 +/- 1560 IFN-gamma binding sites per cell. A single class of high-affinity receptor was observed (Kd = 4.5 +/- 2.5 x 10(-10) M). TNF-alpha did not competitively inhibit 125I-IFN-gamma binding. When FLS were incubated with TNF-alpha (100 ng/ml), there was a paradoxical 49.5 +/- 5.6% increase in the number of binding sites for IFN-gamma (P = 0.001), with no change in the Kd. Unstimulated FLS also expressed 2850 +/- 700 TNF-alpha receptors per cells, with a single Kd consistent with the lower-affinity TNF-alpha receptor (7.4 +/- 0.2 x 10(-10) M). IFN-gamma did not directly interfere with TNF-alpha binding. Preincubation of FLS with 100 U/ml of IFN-gamma resulted in a 28.9 +/- 9.0% increase in TNF-alpha receptor expression (P < 0.008), with no change in the Kd. Low levels of the soluble 55-kD TNF receptor were detected in FLS supernatants. IFN-gamma did not effect soluble TNF receptor production.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Mutual antagonism between interferon-gamma and tumor necrosis factor-alpha on fibroblast-like synoviocytes: paradoxical induction of IFN-gamma and TNF-alpha receptor expression. 839 45


<< Previous 1 2 3 4 5 Next >>

---