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)

A new procedure for rapid isolation of dendritic cells (DC) was devised, involving collagenase digestion of tissues, dissociation of lymphoid-DC complexes, selection of light-density cells, then depletion of lymphocytes and other non-DC by treatment with a mixture of lineage-specific monoclonal antibodies (mAbs) and removal with anti-immunoglobulin-coupled magnetic beads. This enriched population (approximately 80% DC) was further purified when required by fluorescence-activated cell sorting for cells expressing high levels of class II major histocompatibility complex (MHC). The isolated DC were characterized by immunofluorescent staining using a panel of 30 mAbs. Thymic DC were surface positive for a number of markers characteristic of T cells, but they were distinct from T-lineage cells in expressing high levels of class II MHC, in lacking expression of the T cell receptor (TCR)-CD3 complex, and having TCR beta and gamma genes in germline state. Splenic DC shared many markers with thymic DC, but were negative for most T cell markers, with the exception of CD8. A substantial proportion of DC from both thymus and spleen expressed CD8 at high levels, comparable with that on T cells. This appeared to be authentic CD8, and was produced by the DC themselves, since they contained CD8 alpha mRNA. Thymic DC presented both the CD8 alpha and beta chains on the cell surface (Ly-2+3+), although the alpha chain was in excess; the splenic DC expressed only the CD8 alpha chain (Ly-2+3-). It is suggested that the expression of CD8 could endow certain antigen-presenting DC with a veto function.
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PMID:The surface phenotype of dendritic cells purified from mouse thymus and spleen: investigation of the CD8 expression by a subpopulation of dendritic cells. 161 65

A T cell line specific to human type II collagen (CII) was selected and propagated from DBA/1J mice immunized with human CII. The line cells were not reactive to type I or type III collagen of human origin, but they were cross-reactive to bovine, rat, and rabbit CII and they recognized both native and heat-denatured human CII. The cells were reactive to an N-terminal three-quarters fragment of human CII, produced by tadpole collagenase digestion of human CII, but not to a C-terminal one-quarter fragment of human CII. The cells showed Thy-1+, Lyt-1+, Lyt-2-, and L3T4+ phenotypes characteristic of T helper cells or delayed-type hypersensitive cells, determined by the immunofluorescence method. To clarify the role of T cells in the pathogenesis of collagen-induced arthritis, we inoculated this cell line into DBA/1J mice and found that they developed clinical arthritis, albeit at a low incidence. The cells attenuated by x-ray were capable of inducing resistance to the subsequent induction of collagen-induced arthritis of DBA/1J mice. The sera from mice protected by inoculation of the cell line exhibited anti-idiotypic antibody response against conventional and monoclonal anti-CII antibodies. Anti-T cell receptor response may be involved in the mechanism for the protective effect of the cell line against autoimmune murine arthritis.
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PMID:Isolation of T cell line capable of protecting mice against collagen-induced arthritis. 244 73

Giant cell arteritis (GCA) is a common disease in the elderly. It is characterized by focal inflammatory lesions dominated by T lymphocytes and macrophages. The etiology of GCA is, however, still unknown. The aim of the present study was to determine whether lesional T cells represent clonal proliferations, and to characterize adhesion receptors that could be important for recruitment of T cells and antigen receptors involved in their activation. Temporal artery biopsies were obtained from 13 patients presenting with clinical signs of GCA. Immunohistochemistry was used to characterize cell surface receptors on CD3+ T cells in situ in the lesions of eight patients with biopsy-verified GCA. The overwhelming majority of T cells in GCA lesions expressed the TCR alpha beta receptors. In sections from three of eight patients, a small proportion of cells expressing TCR gamma delta was also seen. Almost all T cells expressed the integrin receptors, LFA-1 and VLA-1, as determined by double-staining. To characterize the clonal composition of the lesional T cell population, cells were isolated by collagenase digestion of two lesions and T cells cloned by limiting dilution in the presence of mitogenic antibodies, IL-2 and autologous feeder cells. Rearrangements of the T cell receptor (TCR) genes of the clones were analysed by Southern hybridization using probes for TCR gamma and beta genes. T cell clones established from GCA lesions exhibited heterogeneous rearrangement patterns, indicating a polyclonal origin of the cells. We conclude that GCA lesions contain T lymphocytes that are of polyclonal origin and express integrin-type adhesion receptors. This supports the hypothesis that GCA involves an inflammatory response during which polyclonal T cells adhere to arterial tissue components and accumulate in the developing lesions.
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PMID:T lymphocytes in giant cell arteritic lesions are polyclonal cells expressing alpha beta type antigen receptors and VLA-1 integrin receptors. 838 21

Lymphocytes were extracted from 11 biopsy specimens of oral lichen planus (OLP) by collagenase digestion, and cell lines were expanded with repetitive cycles of stimulation (with phytohaemagglutinin) and rest in media supplemented with interleukin 2. Four OLP lines contained a majority of CD3+CD4-CD8+ cells, in six lines the CD4:CD8 ratio was between 1 and 2, and in one line the CD4:CD8 ratio was 5:1. Limiting dilution of nine lines at 0.3 and 1.0 cells/well resulted in viable wells (putative clones) with plating efficiencies ranging from 0.0 to 18.1 percent and 0.0 to 22.2 percent respectively. The majority of clones were CD3+CD4-CD8+alpha beta+gamma delta-, although three clones were CD3+CD4+CD8-alpha beta+gamma delta- and one clone was CD3+CD4-CD8- and expressed the gamma delta T cell receptor. T cell clones derived from lymphocytes extracted from OLP lesions may be generated and maintained in culture providing opportunity for their further phenotypic and functional characterisation. This strategy may facilitate the identification of a putative oral lichen planus-specific antigen and indicate the frequency of lichen planus-specific T cells within lesions of OLP.
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PMID:Clonal expansion of lymphocytes from oral lichen planus lesions. 848 18

The initiation or exacerbation of psoriasis vulgaris is associated with infections by group A streptococci. T lymphocytes specific for streptococcal antigens or expressing a restricted, for streptococcal superantigens typical T cell receptor Vbeta chain repertoire have been described in psoriatic skin lesions. The aim of our study was, therefore, to clarify whether streptococci-reactive T lymphocytes played a role in the pathogenesis of psoriatic arthritis (PsA), and by which antigens they might be stimulated. Synovial membrane mononuclear cells from patients with PsA and other arthropathies, separated by collagenase digestion, were expanded in interleukin-2-supplemented medium and subsequently cloned in a representative cloning procedure. The T cell lines and about 30% of the T cell clones proliferated in response to preparations of group A streptococci but not to other bacteria as tested by [3H]thymidine incorporation assays. Interestingly, they did not proliferate in response to exotoxin-negative streptococci, but did so in response to the streptococcal pyrogenic exotoxins A and C, which are known to be superantigens. Accordingly, no HLA-DR restriction was seen for the proliferative response. The remaining 70% of the established T cell clones did not react to an antigen of group A streptococci. Our results show that in patients with PsA, osteoarthritis or rheumatoid arthritis a significant number of synovial T lymphocytes were responsive to streptococcal superantigens, but not to conventional streptococcal antigens. A disease-specific role of streptococci-reactive T lymphocytes in the pathogenesis of PsA is, therefore, unlikely.
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PMID:There is no disease-specific role for streptococci-responsive synovial T lymphocytes in the pathogenesis of psoriatic arthritis. 1091 58

We investigated the protein expression of gelatinases [matrix metalloproteinase (MMP)-2 and -9] and collagenases (MMP-8 and -13) in cerebrospinal fluid (CSF) from patients with bacterial (BM, n = 17) and aseptic (AM, n = 14) meningitis. In both, MMP-8 and -9 were increased in 100% of patients, whereas MMP-13 was detectable in 53% and 82% respectively. Three patients with clinical signs of meningitis, without CSF pleocytosis, scored positive for all three MMPs. MMP-8 appeared in two isoforms, granulocyte-type [polymorphonuclear cell (PMN)] and fibroblast/macrophage (F/M) MMP-8. Analysis of kinetic changes from serial lumbar punctures showed that these MMPs are independently regulated, and correlate only partly with CSF cytosis or levels of the endogenous inhibitor, tissue inhibitor of matrix metalloproteinase-1. In vitro, T cells, peripheral blood mononuclear cells (PBMCs) and granulocytes (PMN) release MMP-8 and -9, whereas MMP-13 could be found only in the former two cell types. Using models of exogenous (n-formyl-Met-Leu-Phe, T cell receptor cross-linking) and host-derived stimuli (interleukin-2), the kinetics and the release of the MMP-8, -9 and -13 showed strong variation between these immune cells and suggest release from preformed stocks. In addition, MMP-9 is also synthesized de novo in PBMCs and T cells. In conclusion, invading immune cells contribute only partially to MMPs in CSF during meningitis, and parenchymal cells are an equally relevant source. In this context, in patients with clinical signs of meningitis, but without CSF pleocytosis, MMPs seem to be a highly sensitive marker for intrathecal inflammation. The present data support the concept that broad-spectrum enzyme inhibition targeting gelatinases and collagenases is a potential strategy for adjunctive therapy in infectious meningitis.
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PMID:Gelatinase B [matrix metalloproteinase (MMP)-9] and collagenases (MMP-8/-13) are upregulated in cerebrospinal fluid during aseptic and bacterial meningitis in children. 1664 Jun 49