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)

Although an outwardly rectifying K+ conductance (IK,A) is prominently expressed in human alveolar macrophages, the expression of this conductance in human monocyte-derived macrophages (HMDMs) is rare. We have analyzed the induction of the expression of IK,A in voltage-clamped, in vitro differentiated HMDMs by a number of stimuli which produce either priming or activation of macrophages. Cultures were stimulated with lipopolysaccharide (LPS, 2 micrograms/ml), interleukin 2 (IL-2, 100 U/ml), or combinations of LPS and either recombinant interferon-gamma (gamma-IFN, 10 U/ml), phorbol myristate acetate (PMA, 0.01 or 1 microgram/ml) and platelet activating factor (PAF, 20 ng/ml) for periods of up to 24 hr. Treatment of the cells with either LPS or IL-2 greatly enhanced the frequency of current expression. Treatment with either PMA or gamma-IFN alone did not induce current expression; treatment of the cells with a combination of LPS and either PMA, gamma-IFN, or PAF did not enhance current expression over that observed with LPS alone. The expression of the outwardly rectifying K+ current was observed in 36% (n = 321) of the cells for cultures treated with LPS and 33% (n = 55) of the cells for cultures treated with IL-2. The inactivating outward K+ current was absent in cells which were not treated with either LPS or IL-2. The kinetics of current activation and inactivation appeared identical to that previously described for the transient-inactivating outward current of the human alveolar macrophage. Cycloheximide (1 microgram/ml), an inhibitor of protein synthesis, completely suppressed LPS-induced current expression. No correlation was found between peak current amplitude and cell size in LPS-activated cells expressing the outwardly rectifying K+ current, indicating that current density was not held constant from cell to cell. The coupling of ion channel expression and secretion in individual HMDMs was studied using the reverse hemolytic plaque assay. Although an enhancement of K+ current expression was observed following either LPS or IL-2 treatment, a quantitatively similar and uniform increase in the percentage of either IL-1 or lysozyme-secreting cells was not observed. The frequency of current expression in cells identified as secreting tumor necrosis factor-alpha (TNF-alpha), interleukin 1 (IL-1), or lysozyme was the same or decreased over that observed for nonsecreting cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Lipopolysaccharide induction of outward potassium current expression in human monocyte-derived macrophages: lack of correlation with secretion. 155 35

An adherent cell line was established from the much studied pre-B cell line 70Z/3. The adherent cell line had the morphological features of a macrophage and stained positive for non-specific esterase. In addition, this line expressed high levels of RNA for the macrophage specific enzyme, lysozyme. Although the 70Z/3 macrophage variant has lost the ability to respond to lipopolysaccharide and interferon-gamma by expressing RNA transcripts for immunoglobulin light chain, it exhibited a new response characterized by increased levels of I-A RNA transcripts. Both the pre-B and macrophage variants also expressed RNA transcripts which hybridize to a Hox 2.3 probe. In contrast, transcripts which hybridize to Hox 1.1, 2.1, and 6.1 probes are expressed in the pre-B line but could not be detected in the macrophage.
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PMID:Characterization of a 70Z/3 pre-B cell derived macrophage clone. Differential expression of Hox family genes. 170 3

Clinical trials to evaluate the potential of adoptive immunotherapy in cancer patients have been restricted to the use of lymphoid effector cells. Of the other probably even more important host defense system against tumor growth, the mono-nuclear phagocyte system, only monocytes (mo) have been reinfused which, however, represent immature precursor cells and acquire full functional competence only upon further maturation. This is a report on 7 patients who received autologous macrophages (MO) grown in vitro from blood mo and activated by interferon-gamma (IFN gamma). Mononuclear cells were isolated from whole blood by cytapheresis and cultured for 7 days with 2% autologous serum on hydrophobic Teflon foils. Eighteen house before cell harvest, recombinant human IFN gamma was added at 200 IU/ml. Mo-derived MO were purified by counter-current elutriation. Starting with 10(8) MO cells, therapy was escalated up to the maximal number of MO obtainable from one single preparation cycle. Currently, 26 therapies have been performed with the maximal dose being 1.7 x 10(9) MO per infusion. Except for low grade fever (less than 38 degrees C), MO autografts were well tolerated, with no side effects observed. Biological response was followed by analyzing the serum levels of beta 2-microglobulin, neopterin, interleukin-6, tumor necrosis factor, and lysozyme. While in 3 out of 7 patients serum neopterin increased in response to MO therapy, other biological response parameters remained at pretreatment levels. Radiolabeled MO were shown to first accumulate in the lungs, then to pool into liver and spleen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A new approach to adoptive immunotherapy of cancer using tumorcytotoxic macrophages grown from peripheral blood monocytes. 175 53

To investigate the possible role of endogenous cytokines in the immunopathogenesis of sarcoidosis, a study of cytokines in lymph nodes obtained from patients with active pulmonary sarcoidosis was carried out using immunoperoxidase staining and radioimmunoassays (RIA). Cells stained for interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), which appeared to be CD3+ cells and CD14+ cells, respectively, were seen scattered around granulomas. In contrast, cells positive for interleukin-1 beta (IL-1 beta) were located in CD11c+ cells within granulomas. Lymph nodes of patients with sarcoidosis contained significantly higher amounts of IFN-gamma, TNF-alpha and IL-1 beta than control lymph nodes. The levels of IFN-gamma and TNF-alpha in extracts of lymph nodes were correlated with the histological status of the granulomas. IFN-gamma was detected in all stages, while the highest level of TNF-alpha was obtained from lymph nodes containing many active granulomas. The level of serum IFN-gamma was always lower than in lymph node extract and correlated significantly with either serum angiotensin-converting enzyme or serum lysozyme. Patients with positive gallium-67 uptake or bilateral hilar lymphadenopathy had high levels of either serum IFN-gamma or lysozyme. These results suggest that quantitative analyses of IFN-gamma and TNF-alpha in sera and lymph nodes may serve to elucidate the pathophysiology of sarcoidosis.
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PMID:Detection of endogenous cytokines in sera or in lymph nodes obtained from patients with sarcoidosis. 184 8

Human mononuclear phagocytes can be activated to perform a variety of complex functions by exposure to the immunomodulators, lipopolysaccharide (LPS), interferon-gamma (IFN-gamma) and tumour necrosis factor alpha (TNF alpha). Although such activation often involves the release of various cytokines by monocytes and macrophages, little is known of the effects of such signals on their secretion of lysozyme (LZM). In this study, a reverse haemolytic plaque assay for LZM secretion is coupled with immunocytochemistry for the pan macrophage (CD68) marker, EBM/11. This enabled the direct effects of LPS, IFN-gamma and TNF alpha on the secretion of LZM by individual, immunoidentified human mononuclear phagocytes to be investigated. The overall secretion of this peptide by populations of freshly isolated or 3-day cultured monocytes was augmented by exposure for 6 hr to bacterial LPS, recombinant human IFN-gamma or recombinant human TNF alpha. Extension of the culture period for monocytes from 3 to 7 days prior to use in the assay resulted in higher levels of LZM secretion, which could be further increased by TNF alpha but not by LPS or IFN-gamma. Individual peritoneal macrophages activated by inflammation in vivo were uniform in their augmented LZM responses to TNF alpha, but a small subpopulation of human peritoneal macrophages, which may represent younger 'inflammatory' exudate macrophages, was seen to be preferentially responsive to the LZM-stimulating effects of LPS and IFN-gamma. These studies suggest that (i) secretion of LZM by human mononuclear phagocytes can be regulated by LPS and IFN-gamma, although the effects of these agents may be dependent upon the state of maturation and/or differentiation of the cells, and (ii) TNF alpha is a potent stimulant of LZM secretion by monocytes and macrophages irrespective of cell maturity.
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PMID:Differential effects of LPS, IFN-gamma and TNF alpha on the secretion of lysozyme by individual human mononuclear phagocytes: relationship to cell maturity. 210 46

A murine cell line (BV-2) has been generated by infecting primary microglial cell cultures with a v-raf/v-myc oncogene carrying retrovirus (J2). BV-2 cells expressed nonspecific esterase activity, phagocytic ability and lacked peroxidase activity. Such cells secreted lysozyme and, following appropriate stimulation, also interleukin 1 and tumor necrosis factor. Furthermore, BV-2 cells exhibited spontaneous anti-Candida activity and acquired tumoricidal activity upon treatment with interferon-gamma. Phenotypically, BV-2 cells resulted positive for MAC1 and MAC2 antigens, and negative for MAC3, glial fibrillary acidic protein (GFAP) and galactocerebroside (GC) antigens. Since BV-2 cells retain most of the morphological, phenotypical and functional properties described for freshly isolated microglial cells, we can conclude that J2 virus infection has resulted in the immortalization of active microglial cells.
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PMID:Immortalization of murine microglial cells by a v-raf/v-myc carrying retrovirus. 211 Jan 86

Proximal tubular (PT) epithelial cells express MHC class II (Ia) antigens in immunologically-mediated renal injury. To study the role of PT as accessory cells, we generated several murine PT-like epithelial cell lines by transformation with origin-defective SV40 DNA. These transformed cell lines display typical alkaline phosphatase and gamma-glutamyl-transpeptidase enzyme activity, proliferation to epidermal growth factor (EGF) and sodium-dependent glucose uptake. Clonal lines of transformed tubular cells from both normal C3H/FeJ and autoimmune MRL-lpr mice do not constitutively express Ia antigens or mRNA for class II. However, stimulation with recombinant interferon-gamma(rIFN-gamma) induces Ia mRNA and surface product in the cell lines. These Ia-positive cells can process and present hen egg-white lysozyme (HEL) to antigen-specific Iak-restricted T cell hybrids. Unstimulated tubular cells do not express detectable IL-1 alpha, IL-1 beta, TNA-alpha, or IL-6 mRNA. However, stimulation with IL-1 alpha or LPS induces TNF-alpha transcripts. We conclude that these cell lines have characteristics most consistent with a proximal tubular origin. They also bear characteristics of accessory cells such as processing and presentation of antigen and TNF-alpha gene expression. We speculate that PT have the capacity to participate in the pathogenesis of immune renal injury.
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PMID:MHC class II, antigen presentation and tumor necrosis factor in renal tubular epithelial cells. 240 90

We report the results of a phase I study of the tolerance and biologic activity of intramuscularly (IM)-administered recombinant interferon-gamma (rIFN-gamma). Forty-four patients with metastatic cancer were given rIFN-gamma at doses ranging from 0.01 to 2.5 mg/m2/d for 42 days. The most common side effects were fever, flulike symptoms, night sweats, and granulocytopenia. The maximum tolerated dose was 0.5 mg/m2/d. Administration of rIFN-gamma resulted in modulation of immune system functions, including induction of major histocompatibility complex-associated antigens on blood leukocytes, an increase in blood surface immunoglobulin-bearing B cell and natural killer (NK) cell number, and NK cell cytotoxicity. Serum lysozyme, determined as an estimate of tissue macrophage activity, also increased. Serum assays for anti-interferon antibodies were negative in all patients. Five of eight evaluable patients with lymphoproliferative disorders showed objective evidence of tumor regression consisting of partial responses (two patients), and minor responses (three patients). These data suggest that further phase II studies of IM-administered rIFN-gamma are indicated.
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PMID:Phase I study of multiple dose intramuscularly administered recombinant gamma interferon. 308 21

Two lower-molecular-weight derivatives of recombinant human interferon-gamma (rIFN-gamma) were purified concurrently from a lysozyme-EDTA extract of Escherichia coli cells by immunoaffinity chromatography using a monoclonal antibody (MAb) against a synthetic carboxy-terminal peptide (Lys-131-Gln-146). The two derivatives, 15K rIFN-gamma and 17K rIFN-gamma, were regarded to have been generated at the extraction step. They were successfully separated from each other by using another MAb against the same synthetic peptide with higher binding affinity than the first. The results of protein-chemical analyses indicate that 15K rIFN-gamma and 17K rIFN-gamma lack 15 (Arg 132-Gln-146) and 4 (Arg-143-Gln-146) carboxy-terminal amino acid residues, respectively. All the data suggest that the two derivatives form a noncovalent dimer and that 15K rIFN-gamma binds indirectly to the MAb column via 17K rIFN-gamma.
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PMID:Differential purification by immunoaffinity chromatography of two carboxy-terminal portion-deleted derivatives of recombinant human interferon-gamma from Escherichia coli. 311 44

Macrophage procoagulant-inducing factor (MPIF) is a product of mouse Lyt-1+2- cells that induces macrophage procoagulant activity (MPCA) on mouse peritoneal exudate cells or on the macrophage-like tumor cell line WEHI-265. Supernatants from Sepharose-bound concanavalin A-stimulated cells were fractionated by using DEAE-Sephacel, heparin-Sepharose, and isoelectric focusing. This procedure resolved three different MPIF: MPIF alpha (pI 8.5), MPIF beta (pI 8.8 to 9.2), and MPIF gamma (pI 5 to 5.5). MPIF alpha and beta were small molecules (approximately 14 kD and 20 to 25 kD) as determined by gel filtration on Sephadex G200 and Biogel P100. MPIF beta was sharply resolved as a peak eluting after lysozyme by gel filtration on HPLC columns I-150 and I-125, although SDS-PAGE of the HPLC-enriched material resolved two well-defined bands of 70 and 120 kD and some poorly defined material of 14 kD. Silver staining failed to detect components of MPIF alpha after SDS-PAGE. MPIF gamma activity was associated with material that separated over a broad range (20 to 60 kD and 60 to 200 kD), possibly due to aggregation with other components of the supernatants. Crude supernatants were stable to heating at 56 degrees C for 30 min and pH 2 treatment, although more highly enriched fractions were unstable to these treatments. Heating at 90 degrees C for 5 min totally destroyed MPIF activity. The properties of the two basic MPIF differ from other lymphokines known to affect macrophage function, e.g., colony-stimulating factor, migration-inhibition factor, interferon-gamma, and interleukin 1.
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PMID:Characterization and purification of mouse macrophage procoagulant-inducing factor. 376 May 75


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