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)

The human monocytic cell line U937 was used as a model system to investigate the effects of glucocorticoids on monocytic differentiation. Upon incubation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) (5 x 10(-9) M) for 48 to 72 h, the immature U937 cells ceased to proliferate and became morphologically and functionally macrophage-like. Preincubation of the cells with glucocorticoids (dexamethasone and prednisolone, 10(-7) and 10(-6) M) but not progesterone (10(-6) M) had marked effects: The cells remained in suspension and developed very little cell-cell interaction. This correlated with decreased expression of the surface molecules ICAM-1 and CD18 as determined by fluorescence-activated cell sorter analysis. The TPA-induced ability of the cells to release lysozyme or to generate reactive oxygen radicals (determined as reduction of nitroblue tetrazolium) was markedly reduced. The induction of cyclooxygenase activity and thus the ability to release prostanoids was almost completely abolished. Inhibition of prostanoid synthesis was also observed when the glucocorticoids were administered 24 or 48 h after TPA. The primary step of TPA induction, the activation and translocation of protein kinase C, however, was not affected by glucocorticoids as determined by activity measurements and Western blot analysis. There was no change in the subsequent TPA-induced induction of c-fos. The down-regulation of the differentiation-related oncogenes c-myc and c-myb was the same in cells treated with TPA in the presence or absence of glucocorticoids. Furthermore, no significant effect of glucocorticoids on the TPA-induced growth arrest was observed. Glucocorticoids thus interfere with TPA-induced functions, which are typical for activated macrophages; however, they do not impair the differentiation process and concomitant growth inhibition.
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PMID:Effects of glucocorticoids on the TPA-induced monocytic differentiation. 150 73

We report the selection and characterization of a U-937 subline which is capable of long-term growth in serum-free medium and can be induced to differentiate. The subline (U-937-1SF) can be maintained in standard RPMI-1640 medium supplemented by antibiotics only. As compared to the serum-dependent U-937 parental cell line, U-937-1SF produced lower amounts of lysozyme and elastase and had a decreased surface expression of complement receptor 1 (CD35) and myeloid antigens CDw17 and CD38. Apart from these alterations, the U-937-1SF cells appear to be morphologically, cytogenetically and phenotypically similar to the parental U-937 clone-1 cells. The capacity of U-937 clone-1 cells to undergo phorbol myristic acid (PMA)-, vitamin D3 (VitD3)- and retinoic-acid (RA)-induced differentiation was retained in the U-937-1SF cells as evidenced by the induced growth arrest, development of a monocyte/macrophage morphology and increased expression of differentiation-associated antigens, e.g. CD11b, CD11c, CD14 and CD18. The growth-inhibitory response to cytokines involved in the activation and differentiation of monocytes, IFN-gamma, TNF-alpha, IL-1 beta, IL-6 and GM-CSF, was normal. Our results suggest that the U-937-1SF subline can be used as a serum-free model system for studies on various aspects of monocyte differentiation.
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PMID:Characterization of a U-937 subline which can be induced to differentiate in serum-free medium. 172 6

In the absence of serum, nonpiliated gonococci expressing PII outer membrane proteins (PIIs) adhere to human neutrophils whereas non-PII-expressing (PII-) gonococci do not. After an observation that neutrophils in monolayers bound more gonococci than neutrophils in suspension, we treated neutrophil suspensions with known stimulants of degranulation and measured subsequent gonococcal adherence to suspended neutrophils. The chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fmlp), the potent secretagogue phorbol myristate acetate, and the calcium ionophore A23187 all caused increased adherence of PII+ gonococci, but not PII- gonococci, to neutrophils in a dose-responsive manner. Increased adherence of gonococci to neutrophils was paralleled by increased degranulation of neutrophil myeloperoxidase, lysozyme, and lactoferrin. Inhibition of fmlp-induced neutrophil degranulation by pertussis toxin, the calmodulin inhibitors trifluoperazine and N-5-chloronaphthalene sulfonamide, or the intracellular calcium-binding agent trimethoxybenzoic acid also inhibited fmlp-induced gonococcal adherence to neutrophils. Neither undifferentiated nor myelocytically differentiated HL-60 cells, which possess primary but defective or nonexistent secondary granules, bound PII+ or PII- gonococci. Gonococci did not adhere to human monocytes, monocyte-derived macrophages, lymphocytes, platelets, or erythrocytes, indicating that several receptors, such as the complement receptors CR1, CR3 (CD11b/CD18), and CR4 (CD11c/CD18) or the adherence complex LFA-1 (CD11a/CD18), were probably not involved in gonococcal adherence to human neutrophils.
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PMID:Up-regulation of human neutrophil receptors for Neisseria gonorrhoeae expressing PII outer membrane proteins. 211 69

Cocaine and its derivatives blunted responses of neutrophils (cell/cell aggregation, up-regulation of the receptor for C3bi (CR3, CD11b/CD18), generation of superoxide anion (O2-) and degranulation to various stimuli. The order of potency of these agents was the same as that for local anesthesia: tetracaine greater than bupivacaine greater than cocaine greater than lidocaine. Neutrophil aggregation elicited by the chemoattractant FMLP (10(-7) M) was inhibited by cocaine (10 mM) to 13.6 +/- 6% of control (p less than 0.002); the IC50 was approximately 4 mM. Cocaine and the other local anesthetics not only inhibited the upregulation of CR3 and O2- generation, but also blocked degranulation of cytochalasin B-treated cells. Cocaine (10 mM) reduced beta-glucuronidase and lysozyme secretion to 4.3 +/- 0.7 and 13 +/- 2.2% controls, respectively; its IC50 was 4 mM. Local anesthetics added after ligand/receptor engagement (FMLP) interrupted aggregation and halted generation of O2-. Moreover, local anesthetics rapidly inhibited aggregation, O2- generation, and degranulation elicited by PMA (1 microgram/ml) or the Ca ionophore A23187 (10 microM): the effects of cocaine could therefore not be attributed to unique actions at the FMLP receptor. Peak levels of intracellular Ca2+ ([Ca]i) at 5 to 10 s, and levels of [Ca]i 120 s after FMLP in Fura 2-loaded cells were significantly lower in cells treated with lidocaine, findings that could be explained by enhanced 45Ca2+ efflux from neutrophils. In cells loaded with bis(carboxyethyl)carboxyfluorescine (pH indicator) local anesthetics failed to affect the initial FMLP-induced (0 to 15 s) drop of pHi but inhibited the later (120 s) realkalinization of the cytosol (lidocaine, bupivacaine). Most remarkably, autoradiographs of SDS gels prepared from stimulated, 32P-labeled neutrophils treated with local anesthetics showed no difference from resting cells, either with respect to patterns of phosphorylation and dephosphorylation or their kinetics. Labeling of a 47-kDa protein, a component of the reduced nicotinamide-adenine dinucleotide phosphate-oxidase system, was unchanged. The effects of local anesthetics, which blunt neutrophil responses without affecting protein phosphorylation, suggest that protein phosphorylation is an insufficient signal for neutrophil activation. Inasmuch as cocaine and its derivatives affect cell functions at sites distal to activation of protein kinase C, these agents should prove useful in uncoupling protein phosphorylation from functional responses.
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PMID:Cocaine and its derivatives blunt neutrophil functions without influencing phosphorylation of a 47-kilodalton component of the reduced nicotinamide-adenine dinucleotide phosphate oxidase. 216 79

We have localized several major extracellular matrix protein receptors in the specific granules of human polymorphonuclear (PMN) and monocytic leukocytes using double label immunoelectron microscopy (IEM) with ultrathin frozen sections and colloidal-gold conjugates. Rabbit antibodies to 67-kD human laminin receptor (LNR) were located on the inner surface of the specific granule membrane and within its internal matrix. LNR antigens co-distributed with lactoferrin, a marker of specific granules, but did not co-localize with elastase in azurophilic granules of PMNs. Further, CD11b/CD18 (leukocyte receptor for C3bi, fibrinogen, endothelial cells, and endotoxin), mammalian fibronectin receptor (FNR), and vitronectin receptor (VNR) antigens were also co-localized with LNR in PMN specific granules. A similar type of granule was found in monocytes which stained for LNR, FNR, VNR, CD18, and lysozyme. Activation of PMNs with either PMA, f-met-leu-phe (fMLP), tumor necrosis factor (TNF), or monocytic leukocytes with lipopolysaccharide (LPS), induced fusion of specific granules with the cell membrane and expression of both LNR and CD18 antigens on the outer cell surface. Further, stimulation led to augmented PMN adhesion on LN substrata, and six- to eightfold increases in specific binding of soluble LN that was inhibited by LNR antibody. These results indicate that four types of extracellular matrix receptors are located in leukocyte specific granules, and suggest that up-regulation of these receptors during inflammation may mediate leukocyte adhesion and extravasation. We have thus termed leukocyte specific granules adhesomes.
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PMID:Adhesomes: specific granules containing receptors for laminin, C3bi/fibrinogen, fibronectin, and vitronectin in human polymorphonuclear leukocytes and monocytes. 248 Mar 53

It would be advantageous to prepare models of the neutrophil plasma membrane in order to examine the role of the plasma membrane in transmembrane signal transduction in the human neutrophil and to dissect ligand-receptor interactions and structural changes in the cell surface upon stimulation. A number of investigators have prepared neutrophil membrane vesicles by homogenization, sonication, or centrifugation--techniques that can result in the loss of substantial amounts of surface membrane material, disruption of lysosomes causing proteolysis of membrane proteins, and contamination of the plasma membrane fraction by internal membranes. These limitations have been overcome in the present studies by employing a modification of the method previously developed in this laboratory. Human neutrophils were suspended in a buffer simulating cytoplasmic ionic and osmotic conditions and disrupted by nitrogen cavitation. The resultant cavitate was freed of undisrupted cells and nuclei and then centrifuged through discontinuous isotonic/isoosmotic Percoll gradients, which resolved four fractions: alpha (intact azurophilic granules), beta (intact specific granules), gamma (membrane vesicles), and delta (cytosol). The gamma fraction was highly enriched in alkaline phosphatase, a marker of the plasma membrane. In addition, this fraction contained less than 5% of the amounts of lysosomes (indicated by lysozyme activity) and nuclei (indicated by DNA content) found in intact cells or in unfractionated cavitate. Furthermore, the gamma fraction contained less than 10% of the levels of endoplasmic reticulum, Golgi, mitochondrial, and lysosomal membranes in cells or cavitates, as determined by assays for glucose 6-phosphatase, galactosyl transferase, monoamine oxidase, and Mo1 (CD11b/CD18; Mac-1), respectively. Finally, 75% of the membrane vesicles were sealed, as indicated by assay of ouabain-sensitive (Na+,K+) ATPase activity, and 55% were oriented right-side-out, as determined by exposure of concanavalin A (ConA) receptors and sialic acid residues on the surfaces of the vesicles. These heterogeneous preparations could be enriched for right-side-out vesicles by their selective adherence to ConA-coated plates and subsequent detachment by rinsing the surfaces of the plates with alpha-methylmannoside. This enrichment protocol did not affect the integrity of the vesicles and resulted in populations in which greater than 85% of the vesicles were oriented right-side-out. This procedure thus permits the preparation of sealed, right-side-out membrane vesicles that may be used as valid experimental models of the neutrophil plasma membrane in a variety of functional studies.
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PMID:Preparation and characterization of plasma membrane vesicles from human polymorphonuclear leukocytes. 259 31

We investigated the involvement of polymorphonuclear granulocytes (PMN) and monocytes in cartilage degradation in immune complex-mediated arthritis (ICA). ICA induced with lysozyme-antilysozyme in the murine knee joint is characterized by a major influx of PMNs followed by monocytes and marked cartilage proteoglycan (PG) depletion develops within 2 days. Around 60% of 35S-prelabeled PG is lost at day 2. Influx of cells was manipulated using interleukin-1 (IL-1) receptor antagonist (IL-1ra) or antibodies to adhesion molecules. Cellular infiltrate was analyzed on hematoxylin-stained joint sections. Early systemic treatment with IL-1ra highly reduced PMN influx, whereas monocyte influx was hardly diminished. PG loss was not significantly reduced, declining from 62% in controls to 47% in IL-1ra-treated mice. Total blockade of cell influx was found after intravenous treatment with monoclonal antibodies 5C6 (anti-CD11b/CD18:anti-CR3) or NIMP.R14 (25-30 kDa protein mainly present on PMN) and PG loss was reduced to 5-10%. A similar reduction was observed after prior depletion of circulating PMNs with total body irradiation. Because amounts of IL-1 produced in leukopenic and control arthritic joints are comparable, this suggests that IL-1 is only marginally involved in PG loss in the first phase of ICA. This study indicates that monocytes rather than PMN might be involved in PG loss in this form of arthritis, either directly or by local activation of synovial layer cells of the joint.
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PMID:Monocytes/macrophages rather than PMN are involved in early cartilage degradation in cationic immune complex arthritis in mice. 906 Apr 49

Few human monoblastic cell lines have been characterized to date. We have established the SigM5 cell line from a patient with acute monoblastic leukaemia (FAB M5a). Original leukaemic cells had a karyotype of 47,XY,+8, whereas the cell line showed a stemline clone of 81,XX,Y,Y,1,4,6,7,+8,+8,9,10,10,11,13,16,19[cp], with a minor sideline also present. Cytochemical staining was strongly positive with alpha-naphthylbutyrate acetate esterase, particulate positive with Sudan black and weakly positive for myeloperoxidase. Cells were positive for CD13, CD15, CD18, CD23, CD33, CD38, CD45, CD68 and myeloperoxidase. CD14 expression was 3-15%. SigM5 constitutively secreted interleukin (IL)-2, IL-8, IL-10, tumour necrosis factor (TNF)-alpha, ferritin, lysozyme, N-elastase and neopterin upon stimulation with interferon (IFN)-gamma. Cells expressed the proinflammatory mediator macrophage migration inhibitory factor (MIF). All NADPH oxidase subunits were constitutively present, but nitroblue tetrazolium reduction was only detectable upon activation with IFN-gamma. SigM5 monoblasts were sensitive to arsenic trioxide (As2O3) previously not described to induce apoptosis in monoblastic cells. Differing considerably in morphology, immunophenotype and sensitivity to arsenics from the widely used cell lines U937, HL-60 and THP-1, SigM5 is a new monoblastic cell line useful for studying leukaemogenesis, monocyte differentiation and tumour cell susceptibility to arsenic compounds.
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PMID:Establishment and characterization of an arsenic-sensitive monoblastic leukaemia cell line (SigM5). 1084 31

The two major gram-positive bacterial (GPB) ligands are peptidoglycan (PGN) and lipoteichoic acid (LTA). These polymeric LTA and highly organized PGN contain repeating carbohydrate moieties, which are potential targets for pattern recognition molecules. The major pattern recognition proteins and receptors, which bind GPB, either have a lectin, PGN recognition, collagen or leucine-rich repeat (LRR) domain. The soluble innate immune proteins (IIPs) that bind to PGN and LTA include pulmonary collectins surfactant-associated proteins (SP-) A and D, lectin-like pentraxins C-reactive protein (CRP) and serum amyloid P component (SAP), and sCD14. Membrane-anchored lectin or lectin-like group members include macrophage mannose receptor (MR), complement receptor 3 (CR3, or Mac-1, or integrin CD11b/CD18), scavenger receptor A (SRCL-1), lectin-like oxidized LDL receptor 1 (LOX-1), and GPI-anchored CD14. Although Toll-like receptor (TLR) 2 and 4, and CD14 contain extracellular LRR domains, only TLRs have a cytoplasmic domain for signal transduction. Three of the four recently discovered human PGN recognition proteins (PGRP) have a transmembrane domain, and hence, considered as true receptors for GPB. Since lysozyme is the only known pulmonary enzyme that can lyse bacterial cell wall PGN, other innate immune molecules appear to be responsible for signalling and enhancing the clearance of GPB infection from the lung. Interestingly, pulmonary collectins bind not only to GPB ligands but also to the receptors, CD14 and TLR, and antigen processing cells such as dentritic cells. These complex interactions appear to play major roles in linking innate and adaptive immunity, and maintaining a pathogen-free lung with minimal, or no inflammation.
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PMID:Pulmonary innate immune proteins and receptors that interact with gram-positive bacterial ligands. 1239 17

We analysed a total of 530 expressed genes from the head kidney cells of common carp (Cyprinus carpio) treated by immunostimulants. Sequences of the cDNA clones were compared with sequences in the GenBank database. Immune-related genes identified after in vitro stimulation of carp head kidney cells were: BPI/LBP, C-type lectins, fucolectins, CC-chemokine, CXC-chemokine, CD18, cyclophilin, FcgammaR, G-CSFR, HSP 70, Ig heavy and light chains, NITR, integrin beta2-alpha, Mx, interleukin-1beta, beta thymosin, lysozyme G & C, MHC class II associated invariant chain 1 and 2, granulin, CAAT binding protein and tumour necrosis factor-alpha induced protein. The expression of these immune-related genes may be important for estimating the efficacy of immunostimulants.
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PMID:Identification of expressed genes in carp (Cyprinus carpio) head kidney cells after in vitro treatment with immunostimulants. 1596 69


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