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)

Endothelial cells, separated from the inside of the umbilical vein by collagenase digestion, could clearly stimulate allogeneic lymphocytes to blastogenesis and increased DNA synthesis in mixed lymphocyte endothelial-cell cultures. Many of the characteristics of these mixed cultures were similar to those found in mixed cultures consisting exclusively of allogeneic lymphoid cells; the MLC response. Endothelial cells could also be destroyed in vitro by cells sensitized in mixed lymphocyte cultures. When incubated in the presence of specific HL-A antisera, they were destroyed in non-immune peripheral blood mononuclear cells. These three reactions are thought to be in vitro correlated to some of the events taking place following allografting in vivo.
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PMID:The role of human endothelial cells in allograft rejection. Some in vitro correlates. 13 55

The specificity in the mixed lymphocyte kidney culture (MLKC) of T cell lines and clones derived from human end-stage renal disease (ESRD) kidneys was studied using collagenase dispersed kidney cells compared with lymphocytes as stimulating cells. These experiments were performed because of previous studies in which infiltrating lymphocytes freshly isolated from ESRD kidney tissue at nephrectomy (as well as autologous splenic T cells) were seen to directly generate this lymphoproliferative MLKC response when stimulated with autologous renal cortical cells. In the current studies, histopathologic staining of tissues and suspensions of infiltrating kidney lymphocytes showed predominance of OKT4 labeled phenotypes, and the stimulation indices in MLKC in general showed a direct relationship with the percentage of helper cells seen in the infiltrates. When T cell lines and clones derived from lymphocytes infiltrating the ESRD kidneys were tested in MLKC, there was evidence of kidney-associated, as opposed to lymphocyte-associated (MLC) reactivity using (3H) thymidine uptake as a reflection of a lymphoproliferative response. Several cell lines and clones derived from these T lymphocytes exhibited a dual reactivity. They served as responding cells in the MLKC reaction and completely suppressed a non-specific allogeneic MLC when added as third-party cells. Quantitatively, some clones suppressed when third-party x-irradiated cells were only 5% of the responding cell number in coculture. In addition to the dual reactivity, phenotypic analysis of these same cell lines and clones employing monoclonal antibodies revealed that individual cells expressed both OKT4 and OKT8 determinants. However, approximately 90% of the cells in the MLC enhancing line were labeled with OKT4. These results indicate that there is a complexity in the autologous MLKC response in that cells with both helper/inducer and suppressor/cytotoxic function take part in the reaction. Although delayed-type hypersensitivity to kidney-associated antigens is inferred as a result of these in vitro assays, nonspecific suppression of other Ia-dependent reactions can simultaneously occur.
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PMID:T cell lines and clones preferentially recognizing kidney-associated antigens in end-stage renal disease. 300 32

Rat antiserum (as well as purified IgG and F(ab')2 fragments) raised against cellfree cytosolic extracts (CFE) of an alloimmune cytotoxic T lymphocyte (CTL) clone (B6.1.SF.1) is a potent inhibitor of CTL-mediated cytotoxicity. Inhibition by this antiserum (termed alpha CTLL) occurred during the postbinding lethal hit stages of cytolysis, because it did not inhibit target cell binding, nor did it prematurely dissociate CTL-target cell conjugates; inhibition was observed regardless of the H-2 haplotype of the target cell or CTL employed; inhibition was reversible when pretreated, and washed CTL were used as effectors; and in Ca++ pulse experiments alpha CTLL inhibited cytolysis beyond the Ca++-dependent (lethal hit) stage of cytolysis. This antiserum did not inhibit lysis of P815 cells by activated murine macrophages or by human cytotoxic cells, and extensive absorption of the antiserum on viable thymocytes, normal spleen cells, or CTL did not reduce its blocking activity. CFE prepared from several sources of CTL, including in vivo elicited peritoneal exudate lymphocytes (PEL), secondary MLC-generated CTL, alloimmune splenic T cells, and CTL clones, contained material(s) that inhibited the ability of alpha CTLL to block CTL-mediated cytolysis. The inhibitory activity was not detected in CFE from a variety of noncytotoxic cell sources, including thymocytes, normal C57BL/6 spleen cells, EL4 or P815 tumor cells, macrophages, and helper T cell clones. It was also absent in CFE prepared from human CTL cells. Furthermore, although alpha CTLL neutralizing activity was not detectable in CFE prepared from memory CTL, it rapidly appeared in CTL parallel to the development of cytolytic activity during secondary MLC cultures. The inhibitory material in CTL-CFE appeared to be specific for alpha CTLL antibody, as it did not affect the CTL blocking activity of anti-Lyt-2 or anti-target cell antisera. Finally, CTL-CFE did not contain proteases that degraded the alpha CTLL antibody. By the use of a soluble-phase immunoabsorbent assay, the biochemical properties of materials present CFE derived from CTL and reactive with alpha CTLL antibody were examined. CTL cytosolic material(s) reactive with alpha CTLL IgG was unstable to brief heating (50 degrees C) or acidic pH, but not to high ionic strength buffers. The material was inactivated by treatment with pronase but not by DNase, collagenase, or trypsin. Gel filtration chromatography of CTL-CFE revealed multiple peaks of alpha CTLL neutralizing activity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Studies on the cytolytic attack mechanism of the cytotoxic T lymphocyte (CTL): preparation of antisera against cellfree cytosolic extracts of a CTL clone capable of blocking the lethal hit stage of CTL cytolysis and analysis of the cytolytic structure. 315 7

The RhoA/ROCK-2 signaling pathway is necessary for activated hepatic stellate cell (HSC) contraction. HSC contraction plays an important role in the pathogenesis of cirrhosis and portal hypertension. This study investigated whether aldosterone contributes to HSC contraction by activation of the RhoA/ROCK-2 signaling pathway. Primary HSCs were isolated from Sprague-Dawley rats via in situ pronase/collagenase perfusion. We found that aldosterone enhanced the contraction of a collagen lattice seeded with HSCs. This induced contraction was suppressed by the mineralcorticoid receptor (MR) inhibitor spironolactone, the ROCK-2 inhibitor Y27632, and the angiotensin II type 1 receptor (AT(1)R) inhibitor irbesartan. Moreover, actin fiber staining showed that aldosterone significantly increased actin fiber formation in HSCs. Pre-incubating with spironolactone, Y27632, or irbesartan inhibited the aldosterone-induced actin fiber reorganization. Molecularly, the effect of aldosterone on activation of HSC contraction was mediated by phosphorylated myosin light chain (P-MLC) through the RhoA/ROCK-2 signaling pathway. All these inhibitors had the ability to block aldosterone-induced protein expressions in the RhoA/ROCK-2/P-MLC cascade in HSCs. Taken together, our current study suggests that aldosterone induces contraction of activated HSCs through the activation of the RhoA/ROCK-2 signaling pathway. This finding may provide a potential therapeutic target for control of cirrhosis and portal hypertension.
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PMID:Aldosterone induction of hepatic stellate cell contraction through activation of RhoA/ROCK-2 signaling pathway. 2154 16