Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.17 (lysozyme)
21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a nonviral transformation strategy for the establishment of permanent cell lines derived from the progeny of individual mouse splenic macrophage (M phi) progenitors. These colony stimulating factor-1 (CSF-1)-dependent cell lines possess many features of mature M phi s, including antibody-dependent phagocytic and cellular cytotoxic activities, ability to secrete lysozyme, and expression of the Mac-1 antigen and mRNA for the CSF-1 receptor. It was also possible to immortalize selected clones of splenic M phi s differing in their constitutive antigen-presenting activities with the retention of the antigen-presenting phenotype in the resultant cell lines. The approach described in this report should be useful in obtaining additional cell lines of M phi s expressing other phenotypes of interest.
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PMID:Immortalization of growth factor-dependent mouse splenic macrophages derived from cloned progenitors. 170 81

The recombinant retrovirus J2, which contains the v-raf/mil and v-myc oncogenes, was used to immortalize mouse splenic macrophages that had been cloned in soft agar. When added to freshly harvested colonies, J2 failed to yield cell lines but it immortalized up to 30% of the clones if they had been maintained for at least 4 months in medium containing colony-stimulating factor 1 (CSF-1). All of the cell lines grew in agar in a CSF-1-independent manner, and they produced tumors in nude and syngeneic mice. The cell lines were judged to be macrophage based on morphological criteria and because they secreted lysozyme, were phagocytic for antibody-coated particles, and expressed both the Mac-1 antigen and the CSF-1 receptor. The cell lines could be divided into three groups based on their expression of Ia and their ability to present an antigen to a T-cell hybridoma. The majority of the lines did not constitutively express Ia or present antigen, but a lymphokine did induce Ia in all of the lines, with most of them also acquiring antigen-presenting activity. However, a small proportion of lymphokine-treated lines continued to lack antigen-presenting activity despite their ability to express Ia. The third and smallest group of cell lines constitutively expressed both Ia and antigen-presenting activity. These results show that the J2 recombinant retrovirus is a useful means of immortalizing functionally distinct populations of cloned splenic macrophages.
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PMID:Immortalization of cloned mouse splenic macrophages with a retrovirus containing the v-raf/mil and v-myc oncogenes. 246 Feb 50

Twenty cases of histiocytic sarcoma in 15 female and five male (384 to 722 days of age) hybrid F1 (C57BL/6 x BALB/c) or F2 (F1 x F1) mice were studied for expression of mononuclear phagocyte and other antigens. Histiocytic sarcomas were found most often in liver, uterus, spleen, and lung. Tissues fixed in Bouin's fluid provided preservation of antigen immunoreactivity, using avidin biotin peroxidase complex immunohistochemistry, with monoclonal and polyclonal antibodies. The mononuclear phagocyte antigens, lysozyme and Mac-2 (a galactose-specific lectin that binds IgE), were found in 60-70% of the cases. The receptor for the macrophage colony-stimulating factor (CSF-1), c-fms, was expressed in 2/20 (10%) of the cases. Mouse immunoglobulins were not found in histiocytic sarcoma cells. In uterine histiocytic sarcomas, previously reported as Schwannomas because of their histologic appearance, S-100 protein was not expressed by tumor cells, although they usually expressed Mac-2 and lysozyme. Hyaline droplets were found in the renal tubules of only 2/19 cases. Our studies provide evidence that murine histiocytic sarcoma expresses antigens (Mac-2, lysozyme, c-fms) found in cells of the mononuclear phagocyte series, in contrast to the B-cell origin of many human histiocytic tumors.
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PMID:Expression of mononuclear phagocyte antigens in histiocytic sarcoma of mice. 811 50

Hematopoietic growth factors may be useful in improving the clinical effectiveness of arabinofuranosylcytosine (ara-C). In vitro studies have indicated that interleukin 3(IL-3) and, to a lesser extent, granulocyte-macrophage colony-stimulating factor (GM-CSF), but not G-CSF or M-CSF, may be capable of specifically augmenting the ability of ara-C to kill leukemic myeloid cells by pharmacological and cytokinetic mechanisms including increase of intracellular ara-CTP/dCTP pool ratios and enhanced ara-C DNA incorporation in leukemic blast cells, decrease of IC 90 of ara-C for leukemic colony-forming cells (CFC) as compared with normal CFC growth, and recruitment of quiescent leukemic cells into the cell cycle. In contrast, the combination of ara-C with M-CSF or with the leukemia inhibitory factor (LIF) appears to be useful in overcoming the block in differentiation of leukemic blast, while the effects of GM-CSF and IL-3 on ara-C-induced differentiation appear limited. The combined treatment of human myeloid leukemia cells by ara-C and LIF is associated with down-regulation of c-myc gene expression, transcriptional activation of jun/fos gene expression, and features of functional differentiation (e.g., the capability to reduce nitroblue tetrazolium, to express lysozyme, or to display differentiation-related surface receptors including C3bi and the c-fms protein). On the basis of these in vitro studies first clinical trials are underway that are examining the efficacy of ara-C combinations with these molecules for the treatment of myeloid disorders.
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PMID:Modulation of cytotoxicity and differentiation-inducing potential of arabinofuranosylcytosine in myeloid leukemia cells by hematopoietic cytokines. 846 21

Cells of the mononuclear phagocyte lineage possess receptors for macrophage colony-stimulating factor (CSF-1) encoded by the c-fms protooncogene and respond to CSF-1 with increased survival, growth, differentiation, and reversible changes in function. The c-fms gene is itself a macrophage differentiation marker. In whole mount analyses of mRNA expression in embryos, c-fms is expressed at very high levels on placental trophoblasts. It is detectable on individual cells in the yolk sac around 8.5 to 9 days postcoitus, appears on isolated cells in the head of the embryo around 9.5 dpc, and appears on numerous cells throughout the embryo by day 10.5. The extent of c-fms expression is much greater than for other macrophage-specific genes including lysozyme and a macrophage-specific protein tyrosine phosphatase. Our studies of the cis-acting elements of the c-fms promoter have indicated a key role for collaboration between the macrophage-specific transcription factor, Pu.1, which functions in determining the site of transcription initiation, and other members of the Ets transcription factor family. This is emerging as a common pattern in macrophage-specific promoters. We have shown that two PU box elements alone can function as a macrophage-specific promoter. The activity of both the artificial promoter and the c-fms promoter is activated synergistically by coexpression of Pu.1 and another Ets factor, c-Ets-2. A 3.5kb c-fms exon 2 promoter (but not the 300bp proximal promoter) is also active in a wide diversity of tumor cell lines. The interesting exception is the melanoma cell line K1735, in which the promoter is completely shut down and expression of c-fms causes growth arrest and cell death. The activity of the exon 2 promoter in these nonmacrophages is at least as serum responsive as the classic serum-responsive promoter of the c-fos gene. It is further inducible in nonmacrophages by coexpression of the c-fms product. Unlike other CSF-1/c-fms-responsive promoters, the c-fms promoter is not responsive to activated Ras even when c-Ets-2 is coexpressed. In most lines, production of full length c-fms is prevented by a downstream intronic terminator, but in Lewis lung carcinoma, read-through does occur, and expression of both c-fms and other macrophage-specific genes such as lysozyme and urokinase becomes detectable in conditions of serum deprivation.
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PMID:Regulation of CSF-1 receptor expression. 898 63

The possible role of DNA methylation changes during several commitment steps of immature myeloid precursor cells toward functional, terminally differentiated phagocyte cells has previously been examined in the human myeloperoxidase (MPO) and macrophage colony-stimulating factor/c-fms genes using normal and transformed myeloid precursor cells. The human lysozyme (LZM) gene also provides a very useful model, because its protein synthesis is continuously increased during myelopoiesis and thus most abundant in mature phagocytes. Several shifts toward LZM gene demethylation coincide with upregulation of expression: activation of expression in myeloid precursor cells and in primary cells of acute myeloid leukemia (AML) was associated with demethylation at a CpG dinucleotide within the 5' flanking region; high-level expression in different types of normal mature phagocytic cells was associated with complete demethylation at two additional, intragenic CpG sites. Methylation changes occurring within the lysozyme gene could reflect transcriptional control of gene expression or maintenance of distinct maturation stages during phagocyte development. They correlate with maturational arrest and lysozyme gene expression in acute myeloid leukemias and may thus provide a genetic marker for the blocked differentiation of these neoplastic cells. Similar observations have been made for the MPO and c-fms genes.
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PMID:Cytosine methylation changes during normal hematopoiesis and in acute myeloid leukemia. 913 Jun 86

Cells of the M1D+ murine myeloid leukemic cell line differentiate into macrophages in response to either leukemia inhibitory factor (LIF) or interleukin 6. Previously, it was shown that LIF treatment of M1D+ cells leads to an increased expression of colony-stimulating factor (CSF) receptor mRNA encoded by c-fms. CSF-1, a macrophage growth factor, induces the survival, growth, and differentiation of mononuclear phagocytes but has not been implicated in the regulation of early myeloid cell differentiation. Here we show that low-dose LIF treatment of M1D+ cells results in CSF-1 secretion and CSF-1 receptor up-regulation. CSF-1, when applied alone, induces some M1D+ adherence and the up-regulation of lysozyme M, a macrophage-specific marker. Finally, we show that when applied together, LIF and CSF-1 act synergistically to induce macrophage morphology, phagocytosis, and the expression of the macrophage-specific markers CD11b/Mac-1 alpha chain, lysozyme M, FcgammaRII, and JE/MCP.1. These results indicate that instead of being part of exclusive pathways, as thought until this work, LIF and CSF-1 can function synergistically to further stimulate the early stages of myeloid differentiation.
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PMID:Synergistic effects of colony-stimulating factor 1 and leukemia inhibitory factor in inducing early myeloid cell differentiation. 983 Dec 45

During mouse embryogenesis, macrophage-like cells arise first in the yolk sac and are produced subsequently in the liver. The onset of liver hematopoiesis is associated with the transition from primitive to definitive erythrocyte production. This report addresses the hypothesis that a similar transition in phenotype occurs in myelopoiesis. We have used whole mount in situ hybridization to detect macrophage-specific genes expressed during mouse development. The mouse c-fms mRNA, encoding the receptor for macrophage colony-stimulating factor (CSF-1), was expressed on phagocytic cells in the yolk sac and throughout the embryo before the onset of liver hematopoiesis. Similar cells were detected using the mannose receptor, the complement receptor (CR3), or the Microphthalmia transcription factor (MITF) as mRNA markers. By contrast, other markers including the F4/80 antigen, the macrophage scavenger receptor, the S-100 proteins, S100A8 and S100A9, and the secretory product lysozyme appeared later in development and appeared restricted to only a subset of c-fms-positive cells. Two-color immunolabeling on disaggregated cells confirmed that CR3 and c-fms proteins are expressed on the same cells. Among the genes appearing later in development was the macrophage-restricted transcription factor, PU.1, which has been shown to be required for normal adult myelopoiesis. Mice with null mutations in PU.1 had normal numbers of c-fms-positive phagocytes at 11.5dpc. PU.1(-/-) embryonic stem cells were able to give rise to macrophage-like cells after cultivation in vitro. The results support previous evidence that yolk sac-derived fetal phagocytes are functionally distinct from those arising in the liver and develop via a different pathway.
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PMID:Differentiation of the mononuclear phagocyte system during mouse embryogenesis: the role of transcription factor PU.1. 1038 5

Potential redundancy among members of the CCAAT/enhancer-binding protein (C/EBP) family in myeloid cells is indicated by the ability of C/EBPbeta to replace C/EBPalpha in vivo, by the expression of granulocyte colony-stimulating factor receptor (G-CSFR) on C/EBPalpha(-/-) cell lines, and by our finding that as with C/EBPalpha-estrogen receptor (C/EBPalpha-ER), either C/EBPbeta-ER or C/EBPdelta-ER can induce terminal granulopoiesis in 32D cl3 cells. To assess the consequences of globally inhibiting C/EBPs, we employed KalphaER, containing a Kruppel-associated box (KRAB) transrepression domain, the C/EBPalpha DNA-binding domain, and an ER ligand-binding domain. C/EBPs have a common DNA-binding consensus, and activation of KalphaER repressed transactivation by endogenous C/EBPs 50-fold and reduced endogenous G-CSFR expression. In 32D cl3 cells coexpressing exogenous G-CSFR, activation of KalphaER prevented and even reversed myeloperoxidase, lysozyme, lactoferrin, and C/EBPepsilon RNA induction by G-CSF. In contrast, induction of PU.1 and CD11b, a gene regulated by PU.1 but not by C/EBPs, was unaffected. A KalphaER variant incapable of binding DNA owing to an altered leucine zipper did not affect 32D cl3 differentiation. Transduction of KalphaER into murine hematopoietic progenitor cells suppressed the formation of granulocyte colony-forming units, even in cytokines that enable C/EBPalpha(-/-) progenitors to differentiate into neutrophils. The formation of macrophage and of granulocyte-macrophage colony-forming units were also inhibited, but erythroid burst-forming units grew normally. Thus, in 32D cl3 cells and perhaps normal progenitors, C/EBPs are required for granulopoiesis beyond their ability to induce receptors for G-CSF and other cytokines. One requisite activity may be activation of the C/EBPepsilon gene by C/EBPalpha, as either C/EBPalpha-ER or C/EBPbeta-ER rapidly elevated C/EBPepsilon RNA in 32D cl3 cells in the presence of cycloheximide but not actinomycin D.
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PMID:CCAAT/enhancer-binding proteins are required for granulopoiesis independent of their induction of the granulocyte colony-stimulating factor receptor. 1192 66

Expression of the proto-oncogene c-fos is induced in normal myelopoiesis. However, functions of c-Fos in the process of differentiation towards macrophages are still controversial. To explore the functions, we used the murine myeloblastic leukemia cell line M1. Stimulation of M1 cells with bacterial LPS promotes their terminal differentiation into functional macrophages. Overexpression of c-fos in M1 cells dramatically increased sensitivity of the cells for LPS-induced differentiation and generation of morphologically differentiated cells. However, the overexpression did not modulate phagocytotic functions, surface expression of macrophage markers such as CD16/CD32 (Fcgamma Receptor) and CD54 (ICAM-1), and expression of lysozyme, esterase and c-fms mRNA. Surprisingly, induction of the MHC class II expression on M1 cells after stimulation was inhibited by the overexpression. Expression of CIITA, as an essential transcription factor for the expression, was also reduced in the M1 cells. These results suggest that overexpression of c-fos in differentiating M1 cells perturbs their functional maturation.
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PMID:Overexpression of the c-fos gene perturbs functional maturation of M1 cells into macrophages. 1243 92


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