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)

We examined the immunosuppressor role of the first trimester human decidua on lymphocyte alloreactivity in vitro in order to identify (1) the major cell classes in the decidua mediating the suppressor effect; (2) the stages in the lymphocyte alloreactive responses susceptible to the suppressor effects of the decidua; and (3) the precise nature of the suppressor molecules. Irradiated (2800 R), Ficoll-Paque-separated nucleated cells of the collagenase-dispersed early gestational (6.5-9.5 weeks menstrual age) decidua containing 70-94% typical decidual cells (identified on the basis of distinctive morphology and numerous cytoplasmic or surface markers) or their plastic-nonadherent fractions further enriched for decidual cells (approximately 96% pure) caused a strong dose-dependent suppression of the one way mixed lymphocyte reaction (MLR, i.e., proliferative response measured on Days 3, 4, or 5), when added at the onset of the mixed lymphocyte cultures (MLC). As few as 10(3) decidual cells caused a detectable inhibition of the MLR exhibited by 10(5)-1.5 X 10(5) responder lymphocytes. A smaller degree of suppression was noted with the plastic-adherent fractions of the early decidua (which retained all macrophages and granulocytes, but still included many decidual cells) or unfractionated cells of later gestational (10-13 weeks) decidua containing a higher incidence of leukocytes, granulocytes, and macrophages in particular, or the plastic-adherent fraction thereof, enriched for macrophages. Thus, decidual cells seem to represent an important suppressor cell class in the early gestational human decidua; however, suppression by decidual leukocytes, macrophages in particular, was also evident. The suppressor effect was unrelated to the major histocompatibility phenotype of the responder or the stimulator cells. It was not caused by cell crowding, since an equivalent number of irradiated K562 erythroleukemia cells had little effect on the MLR. The effect was exerted during both the initiation and the progression of the MLR. A delay in the addition of regulator cells progressively minimized the effect on the Day 4 MLR, but did not abolish it completely even when added as late as on Day 3. The major class of mediator molecules was identified as prostaglandins, primarily PGE2, on the basis of the following results: (1) the presence of indomethacin (10(-5) M) or varying dilutions of an anti-PGE2 antibody abrogated this suppression substantially or completely. (2) Addition of pure PGE2 (3 X 10(-7) to 1.1 X 10(-5) M), but not PGF2 alpha, reproduced a dose-dependent suppressor effect.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Suppression of lymphocyte alloreactivity by early gestational human decidua. I. Characterization of suppressor cells and suppressor molecules. 297 89

The erythroid-potentiating activity (EPA) of the tissue inhibitor of metalloproteinase-1 (TIMP-1) was re-examined using ELM-I-1-3, a mouse erythroleukemia cell line, which responded well to erythropoietin. Depletion of pre-existing TIMP-1 from fetal calf serum in culture medium using monoclonal antibody suppressed erythropoietin-induced differentiation as measured by the induction of hemoglobin, commitment assay and globin mRNAs. The removal of TIMP-1 also suppressed the proliferation of ELM-I-1-3 as measured by cell number and de novo DNA synthesis. These changes were reversed by the addition of purified TIMP-1 to the culture medium. Anti-TIMP-1 antibody also blocked both hexamethylene bisacetamide (HMBA)-induced erythroid differentiation and the proliferation of both ELM-I-1-3 and Friend erythroleukemia cells. Considering previous reports analyzing the chemical induction of Friend mouse erythroleukemia cell differentiation, our results suggest that erythropoietin- or HMBA-induced erythroid differentiation might also be coupled with cell proliferation. Our 3H thymidine-uptake experiment shows that TIMP-1 removal was also effective in the inhibition of cell growth of various other cell lines in addition to erythroleukemia cell lines. These results suggest that EPA action of TIMP-1 on erythroid leukemia cell lines is closely related to its activity to promote the cell growth of various cell lines and cells including erythroleukemia cell lines.
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PMID:Erythroid potentiating activity of tissue inhibitor of metalloproteinases on the differentiation of erythropoietin-responsive mouse erythroleukemia cell line, ELM-I-1-3, is closely related to its cell growth potentiating activity. 841 53