Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.21.1 (DNase)
 7,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cloning potential of PHA-treated T cells is significantly enhanced when lymphocyte culture fluid (LCF) from mitogen-treated lymphocytes is added to the soft agar culture system. The mitogens seem to stimulate the release of a lymphocyte colony enhancing factor (LCEF) into the culture medium. A study of the physico-chemical properties of the LCEF revealed that it is a nondialyzable, heat-labile molecule which migrates in the haptoglobin (2--2) post-transferrin region in acrylamide electrophoresis. It is stable to RNase and DNase but labile to papain and trypsin. The LCEF was partially purified from the crude LCF using a sequence of techniques--ammonium sulphate precipitation, DEAE-cellulose and Bio-Gel P-150 chromatography and disc electrophoresis. The mol. wt of the purified LCEF, determined from gel filtration chromatography, was 90,000--110,000.
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PMID:Partial purification and characterization of the human lymphocyte colony enhancing factor (LCEF). 30 93

Tumor culture toxohormone (TCT) obtained from cultures of MBQA mouse tumor cells, a line derived from a methylcholanthrene-induced fibrosarcoma (CBA/J origin), suppressed the mitogenic responsiveness of mouse spleen cells (PHA, LPS) as well as the antibody formation to SRBC in vitro. The immunosuppressive activity of toxohormone was readily inactivated by heating at 100 degrees C or treatment with trypsin, but not by DNase and RNase treatment.
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PMID:Immunosuppression induced by "toxohormone" from mouse tumor cells in culture. 49 45

Addition of increasing concentrations of autologous DNA, but not of allogeneic DNA, in culture media of human lymphocytes induces a parallel increase of thymidine incorporation into leucocytes and of lymphocytes transformation into blast cells. Specificity of DNA action was analysed by different DNase and RNase treatments. DNase or RNase alone neither stimulates blastic transformation of lymphocytes and incorporation of thymidine into leucocytes, nor inhibits PHA-induced stimulations of these cells. However Dnase--but almost not RNase--clearly inhibits thymidine incorporation and blast transformation induced by autologous DNA.
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PMID:Stimulation of human lymphocytes in vitro by purified autologous DNA. 86 12

A flow cytometric procedure measuring the 5-bromo-2-deoxyuridine incorporated into the DNA of cells in S phase was modified to make it compatible with the immunofluorescence labelling of cell surface antigens. The modifications were introduced at the stages of cell fixation and DNA denaturation. Ethanol was replaced by Tween 20-containing paraformaldehyde and hydrochloric acid was used for the denaturation of DNA by bovine pancreatic DNase-I. These two modifications permitted the preservation of immunofluorescence properties and the use of fluorochromes of the phycobiliprotein family such as phycoerythrin and allophycocyanin. This new procedure is suitable for evaluating leucocyte subsets proliferating in vitro following stimulation. As an illustration the immunosuppressive effect of cyclosporin A on PHA stimulated T4-lymphocytes was evaluated.
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PMID:Identification of DNA-replicating lymphocyte subsets using a new method to label the bromo-deoxyuridine incorporated into the DNA. 134 75

After high dose methotrexate (CAS 59-05-2) therapy of children with non-metastatic osteosarcoma the activity of an alkaline DNase with substrate specificity for denaturated DNA increases in lymphocytes and PHA-stimulated lymphocytes. The DNase activity is probably involved in the process of DNA repair. The enzyme has an isoelectric point of pI 5.9, the pH optimum is 8.5, and Mg++ is necessary for activation. Two weeks after the end of the therapy the DNase activity is comparable to the activity of controls. The determination of the alkaline DNase activity can represent a parameter to control side effects of a cytostatic therapy. It is an indirect way to demonstrate therapy induced DNA damage.
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PMID:Increasing alkaline DNase activity with substrate specificity for denaturated DNA after high dose methotrexate therapy. 193 Mar 57

Molecular size chromatography of urine from normal individuals showed two peaks of apparent IL-1 suppressive activities when tested by the murine thymocyte comitogenic assay (mol wt greater than 600 kD and 20 to 60 kD). However, the high molecular weight inhibitory activity disappeared if the concentration of PHA was increased during assay, and the low molecular weight inhibitory activity subsided in the presence of a high concentration of [3H]thymidine. The 20 to 60 kD fractions contained DNase activity which acted on DNA liberated from the considerable number of dying thymocytes during the course of the assay. Thus, incubating the urine fractions with freeze-killed murine T cells, whose DNA was prelabeled with [3H]thymidine, showed the appearance of supernatant [3H]thymidine correlating quantitatively with the DNase activity in the fractions. This indicates that urine DNase together with phosphatase(s) in the thymocyte cultures increase the level of extracellular, unlabeled thymidine, thereby diluting the specific activity of the tracer. These artificial IL-1-inhibitors may explain why urine from both normal and febrile individuals 'inhibits' IL-1 only when tested for thymocyte-activating activity but not when tested for other biological activities.
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PMID:Human urine deoxyribonuclease increases endogenous thymidine in the mouse thymocyte interleukin 1 assay: an artificial interleukin-1 inhibitor. 249 5

To assess the role of decidual cells (DC) in the maintenance of pregnancy, immunosuppressive activity of culture supernatants from human DC were investigated. Dispersed DC suspensions from decidual tissue of early pregnancies were prepared by an enzyme digestion method using collagenase and DNase, and were enriched over 90 per cent without contamination of macrophages and lymphocytes in the fraction, with specific gravity between 1.033 and 1.044 (fraction 2 [Fr2] ) by a Percoll discontinuous density gradient method. The culture supernatants of Fr2 cells suppressed the responses of normal peripheral blood lymphocytes to PHA, MLR, and killer T cell generation at the 50 per cent concentration. To determine the mechanism of the immunosuppressive activity of the culture supernatants, the effect of the supernatants on interleukin-2 and gamma-interferon production, as well as IL-2 receptor expression, on PBL was investigated. The supernatants from 3 x 10(6)/ml of DC cells inhibited not only IL-2 and gamma-INF production, but also IL-2 receptor expression, compared with normal controls. The supernatants also suppressed immunoglobulin (IgG and IgM) production by pokeweed mitogen-stimulated B cells. To purify the suppressor factor from culture supernatants of DC, serum free culture supernatants of 3 x 10(6)/ml of DC, which showed 32 per cent of inhibitory activity on MLR, were applied to gel filtration. Fractions between mw 67,000 and 43,000 suppressed the MLR. These results suggest that DC from decidua of early pregnancy excrete an immunosuppressive factor with a molecular weight between 43,000 and 67,000 daltons.
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PMID:Characterization and analysis of soluble suppressor factor from early human decidual cells. 252 5

Despite some functional impairment of the newborn's T-cell immune system, most infants survive the intrauterine and perinatal period without succumbing to infection or maternal lymphocyte engraftment. The placenta may play a crucial role in protecting the infant from microbial and histocompatibility antigens. Accordingly, we studied phenotypic and functional capacities of placental cells. Placentas were obtained from uncomplicated pregnancies. Matched cord blood and maternal peripheral blood were also obtained in many instances. Fresh minced placental tissue was washed and digested with collagenase and DNase and mononuclear cells were obtained by density gradient centrifugation. The average yield was 10(6) cells/g of tissue with greater than 80% viability. Chromosome analysis of five placental preparations indicated that these cells were of fetal rather than maternal origin. The isolated placental cells consisted of trophoblasts, lymphocytes (74 +/- 3%), monocytes (16 +/- 3%), and granulocytes (8 +/- 2%). E-rosette forming cells (T cells) made up 65 +/- 2% and surface membrane immunoglobulin positive cells made up 8 +/- 1% of the placental mononuclear cells. Fluorescent activated analysis of the mononuclear cells indicated less Leu 4-positive cells (Pan-T) 43 +/- 3%, and less Leu 3-positive (T-helper cells) (25 +/- 2%), than cord and maternal cell preparations. Leu-2, DR, and B1 positive cells were similar to those in cord and maternal blood. Leu 7 and especially Leu 11 positive cells, markers for natural killer cells, were abundant in placental cells, making up 4 +/- 0.7% and 20 +/- 3%, respectively. The Leu 7/Leu 11 ratio of the placental cells was different from either the maternal or cord blood cells. Natural killer activity of placental cells against a K562 natural killer target was low, despite the abundance of cells with NK markers. The K562 activity was low in the placental cells, similar to the low NK activity of maternal and cord cells. Molt 4f killer activity was near normal. Lectin-dependent cytotoxicity using an EL-4 cell target plus PHA was low in placentas, compared to normal, maternal, or cord cell cytotoxicity. Matched samples indicated that LDCC activity was mother greater than cord greater than placenta. Antibody-dependent cytotoxicity (Raji target) of placental cells showed low activity, and again the paired studies indicated that normal controls greater than maternal greater than cord greater than placenta cytotoxicity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Phenotypic and cytotoxic characteristics of the immune cells of the human placenta. 374 13

Experiments of incorporation of a nucleolytic enzyme into human cells cultured in vitro have been carried out with the aim of inducing structural chromosome variations. Human heteroploid cells, either as asynchronous populations or enriched in mitoses, and PHA-stimulated lymphocytes were used as recipients. We found that all these cells when exposed to pancreatic DNAase I encapsulated in liposomes, either of multilamellar (MLV) or of small unilamellar (SUV) type, show an incidence of chromosome damage higher than that induced by the enzyme free in the incubation buffer. Our results indicate that liposomes are suitable vehicles for the transfer of an exogenous nuclease into human cultured cells. The enzyme remains functionally active and interacts with nuclear DNA, giving rise to chromosome lesions.
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PMID:Chromosomal aberrations induced in human cultured cells by liposome-encapsulated deoxyribonuclease I. 382 60

Exposure to soluble protein Ags in vivo leads to abortive proliferation of responding T cells. In the absence of a danger signal, artificially provided by adjuvants, most responding cells die, and the remainder typically become anergic. The adjuvant-derived signals provided to T cells are poorly understood, but recent work has identified BCL3 as the gene, of those tested, with the greatest differential transcriptional response to adjuvant administration in vivo. As an initial step in analyzing transcriptional responses of BCL3 in T cells, we have identified candidate regulatory regions within the locus through their evolutionary conservation and by analysis of DNase hypersensitivity. An evolutionarily conserved DNase hypersensitive site (HS3) within intron 2 was found to act as a transcriptional enhancer in response to stimuli that mimic TCR activation, namely, PHA and PMA. In luciferase reporter gene constructs transiently transfected into the Jurkat T cell line, the HS3 enhancer can cooperate not only with the BCL3 promoter, but also with an exogenous promoter from herpes simplex thymidine kinase. Deletional analysis revealed that a minimal sequence of approximately 81 bp is required for full enhancer activity. At the 5' end of this minimal sequence is a kappaB site, as confirmed by EMSAs. Mutation of this site in the context of the full-length HS3 abolished enhancer activity. Cotransfection with NF-kappaB p65 expression constructs dramatically increased luciferase activity, even without stimulation. Conversely, cotransfection with the NF-kappaB inhibitor IkappaBalpha reduced activation. Together, these results demonstrate a critical role for NF-kappaB in BCL3 transcriptional up-regulation by TCR-mimetic signals.
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PMID:NF-kappa B regulates BCL3 transcription in T lymphocytes through an intronic enhancer. 1453 Mar 44


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