Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.2.2.7 (heparinase)
 1,270 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of rabbit T lymphocytes on rabbit aortic smooth muscle cell (SMC) phenotype and proliferation were investigated in vitro. SMCs seeded at confluent density in primary culture had a volume fraction of myofilaments (Vvmyo) of 49.8 +/- 2.6% after 3 days of culture, not significantly different from that of freshly dispersed cells (Vvmyo, 54.1 +/- 2.1%). Sister cultures of SMCs to which Concanavalin A-activated T lymphocytes or T lymphocyte-conditioned medium was added had significantly lower Vvmyo (35.5 +/- 2.2% and 31.6 +/- 2.3%, respectively) at the same time point. We have previously shown that a decrease in Vvmyo could be induced by the heparan sulfate-degrading activity of living macrophages and by commercial preparations of heparinase. While activated T lymphocytes also completely degraded heparan sulfate-rich 35S-labeled extracellular matrix (an effect inhibited by the addition of 10 micrograms/mL heparin), no heparanase-like activity was detected in T lymphocyte-conditioned medium, indicating that for this cell type SMC phenotypic change is induced by a different mechanism. Incubation of the T lymphocyte-derived cytokine interferon gamma (IFN-gamma) with freshly isolated rat SMCs caused a significant reduction in Vvmyo at day 2 in primary culture from 54.3 +/- 2.1% (control) to 35.4 +/- 3.0%. Furthermore, a neutralizing antibody specific for IFN-gamma removed the effect of T lymphocytes and medium conditioned by them, thus positively identifying IFN-gamma as the T lymphocyte factor responsible for this activity. T lymphocyte-conditioned medium was mitogenic for passaged (low Vvmyo) SMCs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:T lymphocytes affect smooth muscle cell phenotype and proliferation. 762 15

IP-10 is a member of the chemokine family of cytokines and is induced in a variety of cells in response to interferon gamma and lipopolysaccharide. The self-aggregation common to many chemokines, including IP-10, has hindered the identification of a specific IP-10 receptor. Using an IP-10 alkaline phosphatase fusion protein that fortuitously blocks this self-aggregation, we have identified an IP-10 binding site on a variety of cells including endothelial, epithelial, and hematopoietic cells. This binding site has a Kd of 25 nM, is inhibited by recombinant murine or human IP-10, and is dependent on the presence of cell surface heparan sulfate proteoglycans (HSPG). This conclusion is based on the findings that IP-10 binding to cells is: (a) inhibited by heparin and heparan sulfate; (b) sensitive to a 1 M NaCl wash; (c) eliminated by treatment with heparinase and trypsin; and (d) absent on mutant CHO cells that do not express cell surface HSPG. Platelet factor 4 (PF4), but not IL-8, monocyte chemoattractant protein-1, RANTES, monocyte inflammatory protein (MIP)-1 alpha, or MIP-1 beta, can compete effectively with IP-10 for binding to the cell surface. Furthermore, IP-10 shares with PF4 the ability to inhibit endothelial cell proliferation (IC50 = 150 nM). These studies demonstrate specificity in the interaction of chemokines and HSPG, and they define IP-10 and PF4 as a distinct subset of chemokines sharing an HSPG-binding site and angiostatic properties.
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PMID:The IP-10 chemokine binds to a specific cell surface heparan sulfate site shared with platelet factor 4 and inhibits endothelial cell proliferation. 779 Aug 18