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)

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

This study demonstrates the induction of lysozyme mRNA expression in situ in tissue macrophages (M phi) of mice following in vivo stimulation. The resting resident tissue M phi of most tissues do not contain enough lysozyme mRNA to be detected by in situ hybridization using 35S-labeled RNA probes. Following Bacille Calmette Guerin or Plasmodium yoelli infection, however, M phi recruited to liver and spleen hybridize strongly to the lysozyme probe. Within 24 h of infection, cells found in the marginal zone of the spleen begin to produce lysozyme mRNA. This response is also evoked by a noninfectious agent (intravenously injected sheep erythrocytes), and is possibly the result of an early phagocytic interaction. Later in the infection, other cells in the red and white pulp of the spleen, and cells in granulomas in the liver, become lysozyme-positive. Kupffer cells are rarely lysozyme-positive. Lysozyme mRNA levels in liver granulomas remain relatively constant during the infection, and lysozyme is produced by most granuloma cells. This contrasts with tumor necrosis factor alpha (TNF alpha) mRNA, which is produced by fewer cells in the granuloma, and which can be massively induced by lipopolysaccharide administration. The production of lysozyme, previously considered a constitutive function of M phi, is therefore an indicator of M phi activation in vivo, where immunologically specific and nonspecific stimuli both stimulate lysozyme production at high levels in subpopulations of cells occupying discrete anatomical locations.
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PMID:Lysozyme is an inducible marker of macrophage activation in murine tissues as demonstrated by in situ hybridization. 194 Jul 87

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

Although many cytokines have been implicated in the development and persistence of inflammatory immune responses, it is unknown if any of these are important in inflammatory acne. This study investigated the production of the proinflammatory cytokines interleukin-8 (IL-8), IL-1 beta, and tumor necrosis factor alpha (TNF-alpha) by human monocytic cell lines, ThP-1 and U937, and by freshly isolated peripheral blood mononuclear cells from acne patients. Both Propionibacterium acnes and supernatants obtained from 72-h P. acnes cultures could induce significant concentrations of IL-1 beta, TNF-alpha, and IL-8 by both cell lines and by peripheral blood mononuclear cells as determined by enzyme-linked immunosorbent assay. There was no significant difference between acne and non-acne subjects. Endotoxin quantification and addition of polymyxin B to assays indicated no lipopolysaccharide (LPS) contamination. P. acnes supernatant was fractionated into components with molecular weights of < 3,000, < 10,000, and < 30,000 and assayed for the ability to induce IL-8 and TNF production in ThP-1 cells. Nearly 90% of the original activity was found in the < 30,000-molecular-weight fraction, 50% was in the < 10,000-molecular-weight fraction, and only 15% remained in the < 3,000-molecular-weight fraction. The effluent from the < 3,000-molecular-weight fraction contained about 70% activity, indicating that the inducing factor was not retained in the membrane. Incubation of P. acnes supernatant with various concentrations of mutanolysin or lysozyme resulted in a loss of 60% of the original activity. The addition of jimson lectin, which binds peptidoglycan, resulted in a loss of 70% of the activity in a dose-response manner, whereas peanut lectin had little or no effect on the activity. Heating of the P. acnes supernatant to 65 degrees C also had no effect on the activity. Blocking of CD14, a receptor for both LPS and peptidoglycan, reduced cytokine production by > 50%, suggesting that the soluble stimulating factor may be a secreted form of peptidoglycan-polysaccharide.
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PMID:Induction of proinflammatory cytokines by a soluble factor of Propionibacterium acnes: implications for chronic inflammatory acne. 754 39

The expression of c-ets2 is rapidly induced in a variety of myelomonocytic cell lines as they differentiate into macrophages. We find that constitutive expression of c-ets2 in the M1D+ myeloblast leukemic cell line (M1ets2) is sufficient to push these cells to a more differentiated state. The expression of several differentiation-specific genes is upregulated in M1ets2 cells, including those encoding macrophage-specific lysozyme M and tumor necrosis factor alpha, which are involved in bacteriolytic and inflammatory processes, respectively. Transcription factors c-jun and junB, previously shown to induce partial macrophage differentiation when overexpressed in myelomonocytic leukemia cell lines, are also upregulated in M1ets2 cells. The upregulation of junB is the result of a direct interaction of Ets2 with ets binding sites of the junB promoter, since transient or constitutive Ets2 expression in M1D+ cells activates junB transcription via ets binding sites. In addition, transfection of a dominant negative mutant of Ets2, devoid of its transcriptional activation domain, greatly reduces transcriptional activities of the junB promoter in M1ets2 cells. Finally, unlike their parental M1D+ counterparts, M1ets2 cells secrete the macrophage colony-stimulating factor, CSF-1, and are able to phagocytize. Taken together, these results show that when the immature myeloid M1D+ cell line constitutively expresses c-ets2, these cells acquire different functions of mature macrophages.
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PMID:Constitutive c-ets2 expression in M1D+ myeloblast leukemic cells induces their differentiation to macrophages. 894 40

Using a recently described serum-free culture system of purified human CD34+ progenitor cells, we show here a critical cooperation of flt3 ligand (FL) with transforming growth factor-beta1 (TGF-beta1) in the induction of in vitro dendritic cell/Langerhans cell (DC/LC) development. The addition of FL to serum-free cultures of CD34+ cells supplemented with TGF-beta1, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha, and stem cell factor strongly increases both percentages (mean, 36% +/- 5% v 64% +/- 4%; P = .001) and total numbers (4.4- +/- 0.8-fold) of CD1a+ dendritic cells. These in vitro-generated CD1a+ cells molecularly closely resemble a particular type of DC known as an epidermal Langerhans cell. Generation of DC under serum-free conditions was found to strictly require supplementation of culture medium with TGF-beta1. Upon omission of TGF-beta1, percentages of CD1a+ DC decreased (to mean, 10% +/- 8%; P = .001) and, in turn, percentages of granulomonocytic cells (CD1a- cells that are lysozyme [LZ+]; myeloperoxidase [MPO+]; CD14+) increased approximately threefold (P < .05). Furthermore, in the absence of TGF-beta1, FL consistently promotes generation of LZ+, MPO+, and CD14+ cells, but not of CD1a+ cells. Serum-free single-cell cultures set up under identical TGF-beta1- and FL-supplemented culture conditions showed that high percentages of CD34+ cells (mean, 18% +/- 2%; n = 4) give rise to day-10 DC colony formation. The majority of cells in these DC-containing colonies expressed the Langerhans cell/Birbeck granule specific marker molecule Lag. Without TGF-beta1 supplementation, Lag+ colony formation is minimal and formation of monocyte/macrophage-containing colonies predominates. Total cloning efficiency in the absence and presence of TGF-beta1 is virtually identical (mean, 41% +/- 6% v 41% +/- 4%). Thus, FL has the potential to strongly stimulate DC/LC generation, but has a strict requirement for TGF-beta1 to show this costimulatory effect.
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PMID:flt3 ligand in cooperation with transforming growth factor-beta1 potentiates in vitro development of Langerhans-type dendritic cells and allows single-cell dendritic cell cluster formation under serum-free conditions. 926 60

In immature dendritic cells (DCs), major histocompatibility complex class II molecules accumulate in peptide-loading compartments and, during DC maturation, are exported to the cell surface in response to inflammatory stimuli. Moreover, it has recently been proposed that DCs have specific mechanisms of antigen uptake and delivery into major histocompatibility complex class II-loading compartments. B cells bearing a genetically disrupted invariant chain gene (Ii -/-) show alterations in the transport and function of class II molecules. We herein report that DCs derived from Ii -/- H2(k) but not Ii -/- H2(b) mice undergo normal maturation in response to tumor necrosis factor alpha and show a high degree of class II surface expression. Class II molecules are accumulated in cathepsin D- and H2-M-positive compartments in immature Ii -/- DC and, during DC maturation, are exported to the cell membrane as compact dimers. Ii -/- DCs present putative Ii-dependent hen egg lysozyme-derived epitopes to T cells. These data support the existence of Ii-independent molecular requirements for class II transport and peptide loading in DCs.
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PMID:Dendritic cell maturation and antigen presentation in the absence of invariant chain. 944 86

Streptococcus pneumoniae is the most frequent microbe causing middle ear infection. The pathophysiology of pneumococcal otitis media has been characterized by measurement of local inflammatory mediators such as inflammatory cells, lysozyme, oxidative metabolic products, and inflammatory cytokines. The role of cytokines in bacterial infection has been elucidated with animal models, and interleukin (IL)-1beta, IL-6, and IL-8 and tumor necrosis factor alpha (TNF-alpha) are recognized as being important local mediators in acute inflammation. We characterized middle ear inflammatory responses in the chinchilla otitis media model after injecting a very small number of viable pneumococci into the middle ear, similar to the natural course of infection. Middle ear fluid (MEF) concentrations of IL-1beta, IL-6, IL-8, and TNF-alpha were measured by using anti-human cytokine enzyme-linked immunosorbent assay reagents. IL-1beta showed the earliest peak, at 6 h after inoculation, whereas IL-6, IL-8, and TNF-alpha concentrations were increasing 72 h after pneumococcal inoculation. IL-6, IL-8, and TNF-alpha but not IL-1beta concentrations correlated significantly with total inflammatory cell numbers in MEF, and all four cytokines correlated significantly with MEF neutrophil concentration. Several intercytokine correlations were significant. Cytokines, therefore, participate in the early middle ear inflammatory response to S. pneumoniae.
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PMID:Middle ear fluid cytokine and inflammatory cell kinetics in the chinchilla otitis media model. 1008 40

During their final differentiation or maturation, dendritic cells (DCs) redistribute their major histocompatibility complex (MHC) class II products from intracellular compartments to the plasma membrane. Using cells arrested in the immature state, we now find that DCs also regulate the initial intracellular formation of immunogenic MHC class II-peptide complexes. Immature DCs internalize the protein antigen, hen egg lysozyme (HEL), into late endosomes and lysosomes rich in MHC class II molecules. There, despite extensive colocalization of HEL protein and MHC class II products, MHC class II-peptide complexes do not form unless the DCs are exposed to inflammatory mediators such as tumor necrosis factor alpha, CD40 ligand, or lipoplolysaccharide. The control of T cell receptor (TCR) ligand formation was observed using the C4H3 monoclonal antibody to detect MHC class II-HEL peptide complexes by flow cytometry and confocal microscopy, and with HEL-specific 3A9 transgenic T cells to detect downregulation of the TCR upon MHC-peptide encounter. Even the binding of preprocessed HEL peptide to MHC class II is blocked in immature DCs, including the formation of C4H3 epitope in MHC class II compartments, suggesting an arrest to antigen presentation at the peptide-loading step, rather than an enhanced degradation of MHC class II-peptide complexes at the cell surface, as described in previous work. Therefore, the capacity of late endosomes and lysosomes to produce MHC class II-peptide complexes can be strictly controlled during DC differentiation, helping to coordinate antigen acquisition and inflammatory stimuli with formation of TCR ligands. The increased ability of maturing DCs to load MHC class II molecules with antigenic cargo contributes to the >100-fold enhancement of the subsequent primary immune response observed when immature and mature DCs are compared as immune adjuvants in culture and in mice.
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PMID:The formation of immunogenic major histocompatibility complex class II-peptide ligands in lysosomal compartments of dendritic cells is regulated by inflammatory stimuli. 1072 55


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