Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.17 (lysozyme)
 21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neutrophil enzyme elastase is a potent secretagogue of airway secretory cells, and elastase is present in high concentrations in sputum of patients with hypersecretion (e.g., cystic fibrosis, bronchiectasis). Interleukin-8 (IL-8), a recently discovered cytokine with potent neutrophil chemotactic properties in vitro, is also found in the sputum of these patients. We used an isolated tracheal segment in dogs in vivo to study the effect of IL-8 in causing neutrophil accumulation, elastase release, and secretion (by measuring lysozyme concentrations) in the luminal superfusate. IL-8 caused a potent time-dependent neutrophil accumulation at between 3 and 6 h. The effect was significant at 10(-9) and maximum at 10(-8) M. No increase in free elastase, cathepsin G, or lysozyme was detected in the superfusate. Thus, in contrast to previous studies showing that ragweed antigen causes the accumulation of neutrophil elastase which in turn causes lysozyme secretion, IL-8 causes neutrophil accumulation without granule secretion (or subsequent secretagogue activity). The findings were confirmed with dog and human neutrophils in vitro.
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PMID:Interleukin-8 induces neutrophil accumulation but not protease secretion in the canine trachea. 147 6

A novel cationic immune-complex-mediated arthritis (ICA) model was developed in mice. The highly cationic protein lysozyme was coupled to poly-L-lysine (PLL) and injected intra-articularly into the knee joint of the mouse, shortly after systemic administration of specific antibodies. A vehement joint inflammation developed, characterized by severe joint swelling and the influx of predominantly polymorphonuclear (PMN) leukocyte. Unique properties were combined in this protein. First, an excellent retention of the antigen in joint structures was found, facilitating sufficient IC formation in the synovial tissue and at the cartilage surface. Secondly, PLL.lysozyme appeared to be a potent inducer of interleukin-1 (IL-1). Similar IL-1 production was measured at 6 hours, in both immune or nonimmune mice. Neutralization with antibodies against either IL-1 alpha or IL-1 beta revealed that IL-1 alpha was the dominant cytokine. Resident cells were responsible for this IL-1 production since a comparable IL-1 signal was measured after intra-articular injection of PLL.lys in neutropenic mice. We further investigated whether IL-1 and complement factors were involved in the onset of this ICA. Neutralizing the IL-1 production with antibodies directed against IL-1 alpha and beta showed a significant decrease in joint swelling. Complement depletion by cobra venom factor also prevented the onset of arthritis for the greater part. Only a minor swelling remained at 6 hours after eliciting arthritis, which was similar to the swelling after injecting the antigen alone and probably reflects IL-1 mediated inflammation. In this study, the authors show a synergistic action of IL-1 and complement in the onset of cationic ICA. Unique properties of the antigen such as excellent retention and its ability to induce IL-1 are combined within one molecule and make this antigen arthritogenic in the presence of antibodies and complement activation.
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PMID:Cationic immune complex arthritis in mice--a new model. Synergistic effect of complement and interleukin-1. 160 10

Macrophages and granulocytes seem to play a key role in the pathogenesis of bacterial meningitis. Transforming growth factor beta (TGF-beta) leads to macrophage deactivation, as well as to inhibition of cytokine production and of endothelial granulocyte adhesion. We have investigated the influence of TGF-beta on regional cerebral blood flow (rCBF), intracranial pressure (ICP), and brain edema formation during the early phase of experimental meningitis. Rats which were inoculated intracisternally with live pneumococci or with pneumococcal cell wall hydrolyzed by the M1 muramidase (PCW-M) developed an increase of rCBF and ICP within 4 h postintracisternal challenge. A single intraperitoneal injection of TGF-beta 2 but not of TGF-beta 2 vehicle-control prevented the changes of rCBF. Furthermore, TGF-beta 2 significantly reduced the increase of ICP in rats inoculated with PCW-M. Likewise, the elevation of brain water content after intracisternal injection of pneumococci or PCW-M was blocked by pretreatment of rats with TGF-beta 2. TGF-beta 1 exhibited similar inhibitory effects in PCW-M-injected rats. The beneficial effects of TGF-beta 2 on the initial phase after pneumococcal inoculation seem to be tumor necrosis factor alpha- (TNF-alpha) independent since (a) intracisternal or intraperitoneal injection of neutralizing anti-TNF-alpha antibodies did not significantly influence rCBF, ICP, and brain water content in PCW-M-induced meningitis; and (b) TNF-alpha was only occasionally detected at low levels in cerebrospinal fluid at 4 h after PCW-M application.
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PMID:Transforming growth factor beta 2 inhibits cerebrovascular changes and brain edema formation in the tumor necrosis factor alpha-independent early phase of experimental pneumococcal meningitis. 161 60

Expression of the macrophage mannose receptor is inhibited by interferon gamma (IFN-gamma), a T helper type 1 (Th-1)-derived lymphokine. Interleukin 4 (IL-4), a Th-2 lymphocyte product, upregulates major histocompatibility class II antigen expression but inhibits inflammatory cytokine production by macrophages. We have studied the effect of IL-4 on expression of the macrophage mannose receptor (MMR) by elicited peritoneal macrophages. We found that recombinant murine IL-4 enhances MMR surface expression (10-fold) and activity (15-fold), as measured by the respective binding and degradation of 125I-mannose-bovine serum albumin. Polymerase chain reaction analysis of cDNAs from purified primary macrophage populations revealed that MMR, but not lysozyme or tumor necrosis factor alpha, mRNA levels were markedly increased by IL-4. The above effects were associated with morphologic changes. These data establish IL-4 as a potent and selective enhancer of murine MMR activity in vitro. IL-4 induces inflammatory macrophages to adopt an alternative activation phenotype, distinct from that induced by IFN-gamma, characterized by a high capacity for endocytic clearance of mannosylated ligands, enhanced (albeit restricted) MHC class II antigen expression, and reduced proinflammatory cytokine secretion.
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PMID:Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation. 161 62

Chronic granulocytic leukemia is a rare myeloproliferative disorder in dogs. The present study investigated various functions of leukemic granulocytes in a dog that presented with thrombocytopenic purpura, anaemia and a classical leukemic hemogram. All analyses were performed in parallel with a control dog. Purification of the leukemic granulocytes by density gradient centrifugation revealed three neutrophil and neutrophil precursor populations with different densities. Comparison of cell morphology and density showed that cell density increased with increasing maturity. The control dog possessed only one neutrophil population, with a density greater than 1.077. Analysis of cellular contents of the granular enzymes, elastase, myeloperoxidase and lysozyme showed that leukemic neutrophils were quantitatively markedly different from normal neutrophils with respect to enzyme activities. There were no major differences between leukemic and normal cells as regards aggregatory and migratory responses to different stimuli. The phagocytic capacity of the leukemic cells, however, was dramatically increased compared with the control, and exceeded all previously encountered responses in the assay employed. In a similar fashion, superoxide generation and secretion of elastase and lysozyme in response to zymosan and phorbol myristate acetate were substantially higher than in the control dog. Priming of cell function to a level exceeding that normally attainable in neutrophils appears to have taken place in peripheral blood of the leukemic dog. The only endogenous mediator known to prime neutrophil functions to the extent seen in the present case is the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), which is intimately involved in regulation of myelopoiesis in mammals. On the basis of the enzymological and functional findings in the leukemic dog, we hypothesize that a lactoferrin deficiency in leukemic neutrophils leads to enhanced GM-CSF synthesis, which is ultimately the cause of the observed cellular hyperresponsiveness and contributes to the monocytosis seen in the patient.
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PMID:Enhanced granulocyte function in a case of chronic granulocytic leukemia in a dog. 165 Oct 30

Ligation of interleukin 2 (IL2) is known to regulate both protein tyrosine and serine/threonine phosphorylation. A family of leukocyte transmembrane proteins whose cytoplasmic domain exhibits intrinsic protein tyrosine phosphatase activity is collectively called CD45 and is identified by a set of common cell surface epitopes. Although CD45 is known to be a phosphoprotein, it is not known how phosphorylation specifically regulates its function. We therefore identified a cell line, the IL4-dependent line CTLL-2.4, in which CD45 could be phosphorylated in response to addition of IL2. These cells are a variant of an IL2-dependent murine cell line which were selected for long-term growth on IL4 but which retain the ability to proliferate on exposure to IL2. Incubation of CTLL-2.4 in low serum concentrations followed by stimulation with IL2 caused a three- to fivefold increase in the phosphorylation of CD45 in a time- and concentration-dependent manner. CD45 in non-stimulated cells contained one major tryptic phosphopeptide, whereas, after exposure of the cells to IL2, two new phosphopeptides were present in CD45. The pattern of IL2-induced phosphorylation was different from that found following addition of phorbol 12-myristate 13-acetate (PMA) to the cells. Although IL2 induced rapid and potent tyrosine phosphorylation in CTLL-2.4 cells, all of the basal and cytokine-activated phosphorylation of CD45 occurred on serine residues. The IL2-stimulated phosphorylation caused no change in the amount of cell surface CD45 and no alteration of its catalytic activity using an artificial tyrosine phosphorylated substrate-RCM-lysozyme. We speculate that the increase in phosphorylation of CD45 may modify its association with potential substrates. The differences in the phosphorylation patterns induced by IL2 and PMA further suggest that more than one kinase can use CD45 as substrate and that IL2 activates a protein serine/threonine kinase different from protein kinase C.
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PMID:Interleukin 2 stimulates serine phosphorylation of CD45 in CTLL-2.4 cells. 185 Mar 60

High activity of proinflammatory, type II phospholipase A2 (PLA2) was found in synovial fluids (SF) in inflammatory arthritis. In search for the sources of this PLA2, we cultured human articular chondrocytes and cartilage explants from healthy, osteoarthritic and rheumatoid joints. All cultures, unstimulated by cytokines, released PLA2 extracellularly. Cultures obtained from the deep layers of the cartilage released more PLA2 than those obtained from the superficial layers. Deep layer explants released 0.38 to 18.16 pmol/min/mg protein PLA2/day, whereas superficial layer explants released 0.39-3.18 pmol/min/mg/day. Chondrocyte cell cultures continuously released PLA2, in the first day 909-46347 pmol/min/(10)6 cells and after 9-26 days of culture 166-2115 pmol/min/10(6) cells. PLA2 released from chondrocytes was calcium dependent and had optimum activity at pH 7.5. Cycloheximide markedly inhibited its release. Chondrocyte cultures also released muramidase (LZM) but there was no correlation between PLA2 and LZM release. It may be concluded that cytokine unstimulated human articular chondrocytes synthesize and release PLA2 extracellularly which is similar to that found in the SF. Thus, chondrocytes may possibly serve as one of the sources of intraarticular PLA2.
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PMID:Synthesis and release of phospholipase A2 by unstimulated human articular chondrocytes. 225 99

Cells of the mononuclear phagocyte system arise from circulating blood monocytes (MO) that undergo further maturation on leaving the vasculature and migration into the various tissues and body cavities. This terminal differentiation step is also observed in vitro when blood MO are cultured in the presence of serum. Yet, the inducing signals present in serum are not defined. We have established primary cultures from elutriation-purified blood MO and found that the active metabolite of vitamin D3 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) could induce maturation of MO to macrophages (MAC) in the absence of any serum proteins. Cells were cultured for 7 days with AB-group serum or 1,25(OH)2D3, respectively, and MO maturation analyzed by morphology, functional activity, and the expression of lineage-restricted maturation-associated antigens (MAX.1, MAX.3). At an optimal concentration of 10(-8) mol/L, 1,25(OH)2D3 promoted the development of fully differentiated MAC whose phenotype and functional competence in terms of cytokine release (tumor necrosis factor alpha, interleukin-6, fibronectin, and lysozyme) was comparable with MAC grown in serum. In conclusion, our data may add to the immunoregulatory potential of 1,25(OH)2D3, which may play an essential role in the ontogeny of the mononuclear phagocyte system.
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PMID:Induction of human monocyte to macrophage maturation in vitro by 1,25-dihydroxyvitamin D3. 226 41

CD4+ T cell clones were derived from mice immunized to keyhole limpet hemocyanin to characterize the cytokine profiles of newly isolated clones. Surprisingly, several of the clones had an unrestricted profile, producing IL-2, IL-3, IL-4, IFN-gamma, and TNF after either Con A or Ag stimulation. The coproduction of IL-2 and IL-4 was confirmed at the mRNA level. Subclones were derived which contained RNA transcripts for, as well as secreted, both IL-2 and IL-4 thus confirming the clonality of the original T cell clones. CD4+ T cell clones that expressed an unrestricted cytokine profile upon Con A stimulation were also isolated from mice immunized to other Ag (hen egg lysozyme, OVA, or type II collagen). These data indicate that CD4+ T cell clones newly isolated from immunized mice do not necessarily segregate into the Th1 and Th2 subsets. We propose this new murine CD4+ cell subset with an unrestricted pattern of cytokine production be called Th0.
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PMID:A new murine CD4+ T cell subset with an unrestricted cytokine profile. 247 42

This study was designed to evaluate the effects of tetanus toxin (TT) on lysozyme (LZM) activity by the GG2EE macrophage cell line. GG2EE cells spontaneously produced low amounts of LZM, which were mostly secreted into the culture medium. Upon treatment with various cytokines, GG2EE cells exhibited altered LZM activity. In particular, exposure of GG2EE cells to alpha/beta interferon (IFN-alpha/beta) reduced LZM activity, as opposed to treatment with gamma interferon (IFN-gamma) or colony-stimulating factor 1, which potentiated LZM activity. Spontaneous LZM activity of GG2EE cells was not susceptible to TT action; in contrast, when IFN-gamma- or colony-stimulating factor 1-susceptible cells were treated with TT, a significant reduction on LZM activity was observed. The TT inhibitory effect was dose dependent and manifested only after a 6-h incubation of GG2EE cells with TT. Treatment of GG2EE cells with heat-inactivated TT as well as Ibc- and B-IIb-TT-derived fragments was found to be ineffective, while pretreatment with B-IIb- but not with Ibc-TT-derived fragment abrogated the TT effect. Overall, these data indicate the existence of a specific TT-GG2EE cell interaction, leading to selective inhibition of cytokine-induced LZM activity.
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PMID:Selective inhibition of cytokine-induced lysozyme activity by tetanus toxin in the GG2EE macrophage cell line. 250 Dec 19


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