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

---

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

The effects of the i.v. administration of endotoxin (6.25-50 micrograms/mouse on day 13 after tumor implantation) in mice treated orally with lysozyme hydrochloride (100 mg/kg on days 5-12 from tumor implantation) were examined using Lewis lung carcinoma in the C57Bl mouse and MCa mammary carcinoma of CBA mice. On primary tumor growth, endotoxin alone causes a dose-dependent and statistically significant reduction with a nadir on day +2 from endotoxin treatment. Combined with lysozyme, endotoxin causes an effect independent of the dose used, corresponding to the effect caused by endotoxin alone at the dose of 25 micrograms/mouse. No tumor regression was recorded in any of the treated groups. Endotoxin is virtually devoid of effects at the metastatic level. In the same conditions, lysozyme causes a reduction of primary tumor growth and a more pronounced inhibition of lung metastasis formation as expected from its already reported effects. The antitumor activity of endotoxin, unlike lysozyme, can be ascribed to tumor hemorrhagic necrosis due to tumor necrosis factor (TNF) production, as determined in tumor homogenates. Endotoxin does not increase the antitumor effects in mice treated with lysozyme, as expected from the data obtained with the more immunogenic SA1 sarcoma, although lysozyme increased the mitogenic response to ConA of ex vivo isolated splenocytes, in vitro cultured in the presence of IL-2.
...
PMID:Effects of endotoxin in mice bearing solid metastasizing tumors and treated with lysozyme hydrochloride. 140 79

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)
...
PMID:Lipopolysaccharide induction of outward potassium current expression in human monocyte-derived macrophages: lack of correlation with secretion. 155 35

Macrophage-like cell lines were derived from sheep spleens using conditioned medium from L-929 mouse cells as a source of colony stimulating factor. In seven out of ten attempts colonies of macrophage-like cells appeared after 2-3 weeks of culture. The cells were established in culture as cell lines, and survived 120 passages. They were strongly (+ +) positive for non-specific esterase but negative for peroxidase and produced detectable but small amounts of lysozyme (0.21-1.76 micrograms/10(6) cells). Latex particles were actively phagocytosed. Bacteria (Staphylococcus albus, Staphylococcus aureus) attached to the cell surface and were internalized in the presence of specific antibody. Expression of receptors for immunoglobulin and complement varied somewhat between the different cell lines: the proportion of receptor-bearing cells ranged between 9 and 26% FC-receptors, and 10 and 38% for C-receptors. The cell lines displayed a peculiar karyotype as well as protein profile that were different from normal sheep but similar between the different cell lines. Culture supernatants of the cell lines contained a colony stimulating activity which was used to establish further cell lines. They also spontaneously produced an interleukin-1-like activity that had no effect on baseline proliferation of sheep lymphocytes but enhanced their response to PHA (1.7-fold) particularly in conjunction with sheep IL-2 (4-fold). Prostaglandin E2 was produced in a growth-cycle dependent manner: the peak production occurred on the second day (77-140 pg/ml) at 2 x 10(5) cells and declined to 33-50 pg/ml on the eighth day when cell numbers had increased to 2-3 x 10(6). These easily cultured cell lines derived from normal tissue without the introduction of viral DNA should provide a useful source of material for studies of macrophage function in sheep.
...
PMID:The characteristics of macrophage-like cell lines derived from normal sheep spleens. 181 7

We have studied the effects of dietary supplementation with fish oil on immunological parameters in a group of six normal volunteers, four of whom received a fish oil extract (total EPA dose of 2.4 g/day, which is on the lower range of clinically effective doses) for 6 weeks and two of which received a placebo (olive oil) for an identical period of time. Each volunteer was followed up for a period of 23 weeks after the dietary intervention was ended. All volunteers were boosted with tetanus toxoid (TT) at the onset of the trial. Several immune parameters were followed longitudinally, including NBT reduction and lysozyme release to test neutrophil function; lymphocyte subpopulations; mitogenic responses to phytohemagglutinin (PHA), concanavalin A (Con A) and anti-CD3; IL-2 release after PHA and pokeweed mitogen (PWM) stimulation; immunoglobulin and anti-TT antibody (ATT) synthesis by stimulated lymphocytes; and serum levels of immunoglobulins and of ATT. No consistent changes were observed in neutrophil function tests, mitogenic responses to PHA and Con A, and lymphocyte subsets. The mitogenic response to anti-CD3 and the release of IL-2 after stimulation with PHA and PWM appeared reduced as a consequence of fish oil ingestion, and levels of serum immunoglobulins decreased in three of the volunteers receiving fish oil supplementation. The systemic humoral response after the TT booster appeared not to be influenced by the ingestion of fish oil. However, in those subjects who were given fish oil supplementation, the specific in vitro response of their peripheral blood lymphocytes to TT appeared to be compromised at Week 3. This could reflect the need for progressive accumulation of EPA in lymphocyte membranes for the suppressive effect to be detectable, but it could also reflect a differential sensitivity to the effects of fish oil of circulating B lymphocytes vs. bone marrow B lymphocytes. All the parameters apparently affected by fish oil ingestion were also affected by the incubation of normal lymphocytes with EPA in vitro. In conclusion, low doses of fish oil may have a mild immunosuppressive effect affecting both T and B cell functions. These observations stress the need for more extensive trials designed to determine whether immunosuppressive effects can be consistently elicited and for studies aimed at determining the mechanisms by which omega-3 fatty acids affect the immune system.
...
PMID:Immunosuppressive effects of fish oil in normal human volunteers: correlation with the in vitro effects of eicosapentanoic acid on human lymphocytes. 183 5

Compound IX 207-887 is a novel antiarthritic agent which inhibits the release of interleukin-1 (IL-1) from human monocytes and mouse peritoneal macrophages in vitro at concentrations which are achieved therapeutically in human rheumatoid arthritis and in animal models of arthritis. In the present studies IL-1 activity in conditioned media, homogenates or lysates was monitored using four independent assay systems. Biologically active IL-1 was determined by, a) the induction of latent metalloproteinase-release from rabbit articular chondrocytes, which is relatively specific for IL-1 and b) by a sensitive thymocyte proliferation assay. Immunoreactive IL-1-beta was assayed by RIA and ELISA. In all test systems IX 207-887 significantly reduced both biologically active and immunoreactive IL-1 in culture media, whereas the levels of IL-1 in homogenates or lysates were either unaffected or only marginally reduced. The release of other monokines tested, such as interleukin-6 and tumour necrosis factor-alpha, and the secretion of lysozyme were only marginally influenced. IX 207-887 neither affected the adherence of human monocytes nor markedly inhibited IL-1 or IL-2-induced thymocyte proliferation. In the chondrocyte test no IL-1 antagonistic activity of IX 207-887 could be observed. All of these data indicate that IX 207-887 has the novel property of being an inhibitor of IL-1 release.
...
PMID:Inhibition of interleukin-1 release by IX 207-887. 238 8

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.
...
PMID:A new murine CD4+ T cell subset with an unrestricted cytokine profile. 247 42

To study the biochemistry of processing of a soluble protein Ag by an APC, we investigated how 125I-labeled human insulin (HI) is processed in situ by TA3 mouse hybridoma B cells. Fractionation of TA3 cells into their extracellular, plasma membrane-associated and intracellular compartments coupled with the use of HPLC enabled us to analyze several peptides derived from each compartment. One HI peptide found in all three compartments is composed of residues A1-A14 disulfide-linked to B7-B26 (A1-A14/B7-B26). The presence of this peptide in the extracellular compartment likely resulted from digestion of HI by an enzyme(s) released from the APC. Extracellular processing of radiolabeled HI was inhibited completely by unlabeled HI and N-ethylmaleimide, an inhibitor of a previously described insulin-specific protease, partially by lysozyme but not by BSA or OVA. This suggests that the enzyme involved in the extracellular processing of insulin is relatively insulin-specific and gives rise to the A1-A14/B7-B26 peptide. The processing of HI both at the plasma membrane and intracellularly was inhibited by chloroquine, monensin, and NH4Cl, suggesting that both intracellular pH changes and endocytic and exocytic events may be required for these compartments to process insulin. Kinetic analyses revealed that the processing of insulin into the A1-A14/B7-B26 peptide is first detected at the plasma membrane then intracellularly and finally in the extracellular compartment. This unlabeled A1-A14/B7-B26 peptide was purified from the extracellular compartment of TA3 APC by HPLC; when presented by TA3 APC this peptide effectively stimulated pork insulin (PI/I-Ad) specific Th cells to secrete IL-2. These data, taken together with the identification of another processed insulin peptide, A7-A11/B7-B26, have enabled us to elucidate the first steps in the biochemical pathway(s) of processing of insulin as an Ag in a B cell APC.
...
PMID:Processing and presentation of insulin. II. Evidence for intracellular, plasma membrane-associated and extracellular degradation of human insulin by antigen-presenting B cells. 265 61

The class II molecules of the MHC not only bind processed antigenic peptides but also interact with the TCR. This latter interaction is thought to be the basis for allele specific "restriction" of Ag presentation to T cells. The specificity of this interaction is likely due to amino acid differences in a small number of polymorphic or "hypervariable" regions located in the amino terminal domains of the alpha- and beta-chains. We have explored the functional significance of these polymorphic regions in an I-Ak-restricted, hen egg lysozyme specific Ag presentation system in which the measurement of IL-2 production by T cell hybridomas was used as the indicator of TCR recognition of the I-A/Ag complex. Chimeric I-A molecules, in which b allelic residues were substituted in one or more of the polymorphic regions of the A alpha k chain or in which d allelic residues were substituted in one or more of the polymorphic regions of the A beta k chain, were used to examine the contribution of each polymorphic region of the molecule to its function. The results obtained demonstrate that the regions between residues 69 to 76 of the A alpha k chain and the regions between residues 63 to 67 and 75 to 78 of the A beta k-chain exert a dominant effect on the presentation of lysozyme peptides by I-Ak to the T cell hybridomas in our panel. These observations were confirmed and extended by the analysis of Ag presentation by seven serologically selected mutants, all of which have amino acid interchanges in or around the dominant polymorphic regions. The results suggest that the serologically selected mutants fail to present Ag not because they fail to bind the peptide Ag but because the amino acid substitutions destabilize the interaction between the Ia/peptide complex and the TCR. Use of the recently published hypothetical model for class II structure to interpret the Ag presentation results suggests that the dominant polymorphic regions lie across from one another near one end of the alpha-helices that form the two walls of the proposed Ag-binding cleft located on the top surface of the class II molecule. Furthermore, the majority of the amino acids which have been changed in the serologically selected mutants have side chains which are postulated to point up toward the exterior of the molecule and would, therefore, be potential contact residues for the TCR.
...
PMID:I-Ak polymorphisms define a functionally dominant region for the presentation of hen egg lysozyme peptides. 278 33

Intravenous (i.v.) injection of an antigen before immunization has been shown to be a potent way to induce suppression at the T-cell level. In this study we demonstrate an almost complete suppression of arthritis (using antigen-induced arthritis as a model) by i.v. injection of 100 micrograms hen egg lysozyme (HEL) 7 days before immunization. Underlying mechanisms, including suppression by CD8+ T lymphocytes, suppression by T-helper 2 (Th2) or anergy of antigen-specific T lymphocytes, were studied. In vivo treatment with either anti-CD8 or anti-interleukin-4 (IL-4) could not abrogate i.v.-induced tolerance. Lymphocyte stimulation assays showed reduced antigen-specific proliferative responses and IL-2 production in tolerized mice. The possible role of soluble suppressive cytokines was examined in vitro by adding anti-IL-4, anti-IL-10 or anti-transforming growth factor-beta (TGF-beta). Neutralization of these factors could not diminish suppression. Finally, anergy of antigen-specific T lymphocytes was tested as a possible mechanism for i.v.-induced tolerance. Results demonstrated that reduced proliferative T-cell responses were reversible: incubation of tolerized lymph node cells for 5 days in added recombinant (r)IL-2 fully restored proliferative capacity back to normal. We therefore conclude that the main mechanism of i.v.-induced tolerance in our model is anergy of antigen-specific T lymphocytes.
...
PMID:Anergy of antigen-specific T lymphocytes is a potent mechanism of intravenously induced tolerance. 752 88

Oral tolerance was generated to hen egg white lysozyme in the mouse or to guinea pig myelin basic protein in the rat by a low-dose (1 mg) or a high-dose (5-20 mg) feeding regimen. High doses of antigen induced tolerance characterized by anergy with little or no active suppression and increased secretion of interleukin 4 (IL-4). Anergy was shown by an increase in frequency of IL-2-secreting cells following culture in recombinant IL-2. Low doses of antigen induced tolerance characterized by antigen-driven active suppression with increased secretion of transforming growth factor beta (TGF-beta) and IL-4 and minimal anergy. Without further immunization, spleen cells from animals orally tolerized by both regimens secreted increased levels of IL-4 and TGF-beta in an antigen-specific manner. Animals fed high doses secreted more IL-4 and less TGF-beta, whereas those fed low doses secreted more TGF-beta and less IL-4. These results demonstrate that the two feeding regimens induced cell populations that differed in their cytokine secretion profile and their capacity to actively suppress in vitro and to induce anergy. Our results provide a basis for distinguishing different forms of antigen-driven peripheral tolerance and have important implications for orally induced antigen-specific modulation of human autoimmune diseases.
...
PMID:Induction of anergy or active suppression following oral tolerance is determined by antigen dosage. 802 35


1 2 3 4 5 6 Next >>

---