Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The shape and function of adherent cells cultured from rheumatoid synovial membranes are influenced by immune cells, and their products. The synovial cells produce collagenase and prostaglandin E2 (PGE2), the levels of which are increased when the cells are incubated with the monokine, mononuclear cell factor/interleukin 1. The majority of adherent synovial cells are fibroblastlike in appearance and synthesize collagens and fibronectin; the synthesis of collagens and fibronectins are also increased by a monocyte factor. In the present study we found that the fibroblastlike cells expressed major histocompatibility complex class II (Ia-like) antigens after initial dispersion from the synovial membrane. Monocyte lineage antigens were detected on some round cells in early passage, but no T lymphocytes were identified in established cultures. There was loss of Ia expression on the fibroblastlike cells with age and passage in culture. The addition of the lymphokine, gamma interferon (recombinant), induced class II antigen (DR and DS/DQ) expression in early or late passage cells in a time- and dose-dependent manner and required protein synthesis. Furthermore, the adherent synovial fibroblastlike cells continued to be Ia-positive when examined as long as 10 d after the removal of gamma interferon. Ia expression was also induced by gamma interferon in normal skin fibroblasts. Synovial cells that could be induced to express Ia also bound a monoclonal antibody to type III collagen (a fibroblast marker). Gamma interferon, while inducing Ia expression, decreased the binding of type III collagen antibody on unstimulated as well as monokine-stimulated cells. Analysis of [3H]proline-labeled medium by SDS polyacrylamide gel electrophoresis showed that gamma interferon decreased the synthesis of type I and III collagens and fibronectin by adherent synovial cells in a dose-dependent manner. These findings suggest that Ia expression by synovial tissue cells is not cell-specific, but reflects one or several related events, such as the degree of T lymphocyte infiltration, the presence of factors that stimulate gamma interferon release, or an increased sensitivity of the cells to gamma interferon. Whereas the synthesis of class II antigens is enhanced by the lymphokine gamma interferon, and a monocyte factor(s) stimulates collagen, collagenase and PGE2 synthesis by the same cells, gamma interferon inhibits basal and monokine-induced collagen synthesis. Thus, lymphokines and monokines may influence the extent of fibrosis as contrasted to matrix destruction at various stages of the rheumatoid lesion by affecting the function of fibroblastlike synovial cells.
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PMID:Influences of gamma interferon on synovial fibroblast-like cells. Ia induction and inhibition of collagen synthesis. 299 65

Islets from male B10.BR mice (H-2k) were isolated by the collagenase technique, handpicked with a Pasteur pipette, and incubated (either intact or after dispersion with Dispase) for 0, 3, 5, 7, 10, or 14 days in tissue culture medium supplemented with either lymphokine supernatants or recombinant murine interferon-gamma. Islets and single cells were examined for IAk molecules by use of indirect immunofluorescence. Ia-positive islet cells were identified on the surface of islets incubated with 5-10% lymphokine for greater than 4 days or with 10, 100, or 1000 ng/ml interferon for greater than 6 days. Islets incubated in unsupplemented medium were Ia negative. Incubation with 5% lymphokine induced Ia expression on 10-40% dispersed islet cells cultured for greater than 9 days. Dual immunofluorescent staining for Ia and insulin revealed that Ia-positive cells included both beta- and non-beta-cells.
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PMID:Interferon-mediated induction of Ia antigen expression on isolated murine whole islets and dispersed islet cells. 309

Pinocytosis and prostaglandin E2 production are two major functions of the mononuclear phagocyte system. The goal of this study was to compare the pinocytosis of horseradish peroxidase and the prostaglandin E2 production between the hepatic and peritoneal resident macrophages in the mouse. Hepatic resident macrophages were isolated by collagenase digestion, differential centrifugation and adherence. Peritoneal resident macrophages were isolated by peritoneal cavity washing followed by adherence. Horseradish peroxidase was endocytosed by hepatic macrophages at a significantly higher rate (118 +/- 12 ng/10(6) cells/60 min) than by peritoneal macrophages (21 +/- 4 ng/10(6) cells/60 min). Prostaglandin E2 production was measured in the culture medium of unstimulated and lymphokine-stimulated hepatic and peritoneal resident macrophages. Prostaglandin E2 concentration in the culture medium of unstimulated peritoneal macrophages was 36.6 +/- 26.8 ng/ml after a 24 h incubation. It was increased by 83 p. 100 in presence of a lymphokine-enriched secondary mixed lymphocyte culture supernatant. In contrast, hepatic macrophages did not produce any significant amount of prostaglandin E2, even if they were incubated in presence of lymphokines. This study shows that hepatic resident macrophages have a higher pinocytic capacity than peritoneal resident macrophages, suggesting that the role of the liver in the clearance of gut-derived antigens is not only due to its portal irrigation but also to the presence of macrophages highly differentiated in their endocytotic properties. The lack of prostaglandin E2 production in hepatic macrophages, in basal conditions as well as after lymphokine-stimulation, suggests that these cells play a minor role in the regulation of the immune response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Comparative study of pinocytosis and the production of prostaglandin E2 by hepatic and peritoneal resident macrophages in mice]. 386 Apr 55

Two different approaches were used to examine the role of B cells in the stimulation of syngeneic MLR. The relative inability of spleen and peritoneal exudate cells from B cell deficient mice, treated with anti-mu from birth, to serve as stimulator cells in SMLR was previously shown in SJL mice and confirmed in BALB/c mice in the present studies. Preincubation of cells from anti-mu treated mice with serum Ig does not enhance their ability to stimulate. Upon stimulation with normal spleen cells responses from anti-mu treated mouse T cells are not deficient. Responses of thymus cells from neonates and from adult cortisone-treated mice are also much higher when the splenic stimulator cells come from normal rather than from anti-mu treated mice. The deficiency of the stimulator cells from anti-mu treated mice is in the high density cell population as obtained after BSA gradient fractionation of collagenase treated lymph node or spleen fragments. Low density populations from anti-mu treated and normal mice stimulate equally well. Addition of exogenous IL-2 to the cultures enhances the syngeneic MLR to all stimulator populations and allows stimulation by spleen cells from anti-mu treated mice. It is concluded that, while B cells represent the major stimulator cell population in whole spleen cell suspensions, other accessory cells (dendritic cells?) are more efficient, possibly synergize with B cells by producing IL-1, but usually represent only a minor subpopulation. The other approach concerns the effectiveness of SMLR stimulation by several tissue culture, cloned B lymphoma cell lines, and by a transplantable BALB/c B lymphoma. Of the five stimulating lymphoma cell lines only one stimulates approximately as well in the absence as in the presence of polyethylene glycol. These latter cells (A20.1.11) can also stimulate T cell proliferation and IL-2 production in the absence of Ia+ accessory cells in the responding population and, therefore, either produce their own IL-1 or are able to bypass the requirement for this lymphokine.
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PMID:Role of B cells in the stimulation of syngeneic mixed lymphocyte responses. 624 30

Blood mononuclear cells from patients with rheumatoid arthritis produce the lymphokine, leukocyte inhibitory factor (LIF) in response to collagens in vitro, and blood monocytes release prostaglandins (PGE2) and a factor, mononuclear cell factor (MCF) which stimulates collagenase and PGE2 production by cultured synovial cells. We therefore examined the effect of collagens on the production of PGE2 and MCF. Blood mononuclear cells from 6 patients with rheumatoid arthritis and 6 normal subjects were cultured in native human types I, II, or III collagen-coated tubes, or with streptokinase-streptodornase (SK-SD), and the supernatant media derived from these cultures analyzed for the presence of MCF, PGE2, and LIF. Types II and III collagens, as well as SK-SD, markedly stimulated MCF production by the cells from all 12 subjects (MCF activity, expressed as a mean stimulation index (SI) +/- SEM, was 43 +/- 12 for type II, 33 +/- 7 for type III, and 37 +/- 23 for SK-SD). Type I collagen was less stimulatory (mean SI 10 +/- 7). Cells from the patients with rheumatoid arthritis, but not the normal subjects, produced LIF in response to types II or III collagens but not to type I collagen. PGE2 production by blood mononuclear cells paralleled that of MCF, although abrogation of PGE2 release with indomethacin did not reduce MCF production. alpha chains purified from denatured collagens also stimulated MCF production. Using cells from patients with rheumatoid arthritis, type II collagen stimulated production of all three factors in the presence of polymyxin B or fibronectin-depleted serum, suggesting, respectively, that neither endotoxin nor fibronectin were responsible for their generation. Monocytes, purified from normal blood by an adherence technique, but not lymphocytes depleted of monocytes, released MCF and PGE2 when cultured with type II collagen. These results demonstrate that collagens can act as ligands to stimulate monocytes, as well as antigens to stimulate sensitized lymphocytes, to produce soluble factors that may contribute to the destruction of connective tissue.
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PMID:Collagens act as ligands to stimulate human monocytes to produce mononuclear cell factor (MCF) and prostaglandins (PGE2). 630 48

Rat pulmonary parenchymal tissue was disaggregated into a single cell suspension by treatment with collagenase. A cell population enriched for lung lymphocytes was separated by depletion of adherent cells on a Sephadex G-10 column: 16.7 +/- 2.7 X 10(6) cells per animal were recovered. On the basis of cytochemical and morphologic criteria, the separated cells contained greater than 80% lymphocytes, with a viability of 80-90%. The distribution of lymphocyte subpopulations was determined by indirect immunoperoxidase staining with appropriate monoclonal antibodies. Separated lung lymphocytes exhibited a proliferative response in vitro to phytohemagglutinin and concanavalin A. Supernatants from lung lymphocytes stimulated with concanavalin A contained lymphokine activity that could be demonstrated in a leukocyte procoagulant activity assay.
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PMID:Separation and characterization of lymphocytes from rat lung parenchyma. 652 82

Leukoregulin, a 50-kDa T lymphocyte-derived cytokine, influences the synthesis of collagenase, stromelysin-1, collagen, and hyaluronan in human fibroblasts and is thus a determinant of extracellular matrix economy. We studied the effect of leukoregulin on the expression of plasminogen activator inhibitor type 1 (PAI-1) in human orbital and dermal fibroblasts. The lymphokine upregulated 35S-labeled PAI-1 protein expression in orbital fibroblasts in dose-dependent manner. The effect on extracellular matrix-associated PAI-1 evolved over several hours and was maximal at 10 h, when levels were 75-fold higher than controls, and then fell by 24 h. Leukoregulin treatment increased prostaglandin E2 production in orbital cultures after 24 h. When this increase was blocked with indomethacin, peak PAI-1 levels were maintained. Northern analysis demonstrated a substantial induction of steady-state PAI-1 mRNA levels within 6 h of treatment in orbital cultures. In contrast, leukoregulin lowered PAI-1 protein levels dramatically in skin fibroblasts from the abdominal wall. With regard to PAI-1 expression, it would appear that the anatomic site of origin of fibroblasts is a crucial determinant of the cellular response to leukoregulin.
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PMID:Leukoregulin induces plasminogen activator inhibitor type 1 in human orbital fibroblasts. 765 18

The aim of the present study was to investigate whether women with endometriosis displayed a decreased lymphokine-activated killer (LAK) activity. In 15 women with and 7 women without endometriosis the cytotoxicity against four different tumor cell lines--K562, the endometrium carcinomas AN3CA and RL95, the natural-killer (NK)-resistant Daudi cell line--was investigated, using either freshly isolated peripheral blood mononuclear cells (PBMC) or recombinant interleukin (IL)-2-stimulated PBMC. In 5 additional women collagenase-DNase-digested endometrium was used, to investigate whether recombinant IL-2-activated lymphocytes displayed an increased cytotoxicity against fresh and cultured endometrial cells. The cytotoxicity of unstimulated PBMC toward K562, AN3CA and RL95 target cells was decreased in women with endometriosis compared to women without endometriosis (p < 0.05, for all). After recombinant IL-2 stimulation the cytotoxicity toward the four different target cells increased significantly, both in women with and without endometriosis. There was no difference in LAK-mediated cytotoxicity against the four tumoral cells between women with and without endometriosis. Significant LAK activity was demonstrated against both fresh and cultured (72 h) endometrial cells. The cytotoxicity of autologous lymphocytes against cultured endometrial cells was 31.0 +/- 17 versus 67.4 +/- 5.8%, using lymphocytes cultured in medium without and with recombinant IL-2, respectively (paired t test, p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lymphokine-activated killer activity in women with endometriosis. 800 50

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)
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PMID:Susceptibility of renal tubular cells to lymphokine-activated killer (LAK) cells: application of culture system using a collagen gel matrix. 809 21


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