Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tilmicosin is a semi-synthetic macrolide antibiotic, currently approved for veterinary use in cattle and swine respiratory disease, and is in development for use in poultry mycoplasma air sacculitis. In order to provide an understanding of clinical efficacy, the in vitro interaction of tilmicosin with three types of chicken phagocytes (MQ-NCSU macrophages, monocyte-macrophages, and heterophils) was evaluated. After incubation with radiolabeled tilmicosin, uptake was determined and expressed as the ratio of the cellular (Cc) to the extracellular (Ce) drug concentration (Cc:Ce). Tilmicosin was avidly accumulated by heterophils (Cc: Ce 138 at 4 h incubation vs 32 and 66, respectively, in MQ-NCSU and monocyte-macrophages) with 61 to 88% localized in the lysosomes. Uptake was dependent on cell viability, temperature, and pH, but was not influenced by metabolic inhibitors. However, phagocytosis of Pasteurella multocida and lipopolysaccharide exposure increased tilmicosin uptake by the chicken phagocytes. Upon removal of extracellular tilmicosin, 50% of the intracellular tilmicosin was effluxed within the first 30 min, but after 4 h of incubation in antibiotic-free medium, 30% remained cell-associated. Opsonized P. multocida significantly enhanced the release of tilmicosin from all three types of chicken phagocytes. Tilmicosin uptake was observed to increase lysosomal enzyme (acid phosphatase, lysozyme, avidin, and beta-glucuronidase) production. Finally, neutrophils were shown to transport and efflux bioactive tilmicosin in a test system measuring both neutrophil chemotaxis under agarose and a bioassay measuring inhibition of bacterial growth in the presence of antibiotic in agar. These in vitro observations of cellular pharmacology suggest a complex interaction between phagocytes and tilmicosin that contribute to clinical efficacy.
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PMID:Intracellular accumulation, subcellular distribution, and efflux of tilmicosin in chicken phagocytes. 977 59

In vivo effects of Yersinia enterocolitica 0:3 lipopolysaccharide (prepared from bacteria grown at 25 degrees C and 37 degrees C) were investigated after intraperitoneal (i.p.) and intraarticular (i.a.) injection in rats during 30 days of examination. The persistence of endotoxin in the peritoneal and the synovial cavities was demonstrated by the immunofluorescence technique. Peritoneal and synovial exudative cell infiltration, as well as changes in some parameters (glycolytic and acid phosphatase activity, and killing ability of peritoneal cells; lactate dehydrogenase concentration in synovial fluid) were studied. The results indicated that endotoxin could persist longer in the synovial than in the peritoneal cavity.
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PMID:Persistence and in vivo effects of Yersinia enterocolitica 0:3 endotoxin in rats. 1043 58

In order to explore the depressant action of ambroxol, a bronchial expectorant, on the activated alveolar macrophage responses, its effect on lipopolysaccharide (LPS)- or N-formyl-methionyl-leucyl-phenylalanine (fMLP)- stimulated free radical production and granule enzyme release by rat lung alveolar macrophages was investigated. Ambroxol attenuated the 100 ng/ml LPS- or 1 microM fMLP-stimulated superoxide, H(2)O(2)and nitric oxide production and releases of acid phosphatase and lysozyme by alveolar macrophages. Ambroxol attenuated phorbol myristate acetate-stimulated superoxide and nitric oxide production that was inhibited by 100 nM staurosporine. N,N-dimethylsphingosine (DMS, 4.5 and 9 microM) alone stimulated superoxide production by macrophages, while 45 microM of the compound did not show a stimulatory effect. However, DMS decreased nitric oxide production in a dose-dependent manner. Ambroxol did not alter the DMS effect on free radical production that was affected by 10 microM genistein. A preincubation of macrophages with ambroxol (10 and 100 microM), staurosporine and genistein attenuated the elevation of [Ca(2+)](i)caused by LPS. The results suggest that ambroxol exerts a depressant effect on LPS- or fMLP-stimulated free radical production and granule enzyme release by rat alveolar macrophages, which may be attributed to its inhibitory action on the activation process, protein kinase C, but its action on protein tyrosine kinase is not suggested.
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PMID:Depressant effects of ambroxol on lipopolysaccharide- or fMLP-stimulated free radical production and granule enzyme release by alveolar macrophages. 1054 83

This study was designed to evaluate the effects of voluntary exercise on macrophage and lymphocyte functions in mice. Male A/He inbred mice aged 19 weeks were divided into two groups: a group given voluntary exercise and a control group (n = 10 in each group). Exercise consisted of spontaneous running in wheels for 8 weeks (3 days week-1). Glucose consumption of peritoneal macrophages in the exercise group during incubation up to 72 h was significantly higher than that in the control group (70 and 13%, respectively). Also, activities of acid phosphatase (APH) (10.75 +/- 0.37 IU), beta-glucuronidase (GLU) (1.55 +/- 0.07 IU) and lactate dehydrogenase (LDH) (43.3 +/- 0.7 IU) in the peritoneal macrophages in the exercise group was significantly increased (P < 0.01). Compared with the control group, the exercise group had a significant increase of about twofold in macrophage production of nitric oxide (NO2-) stimulated by lipopolysaccharide (LPS) (11.1 +/- 0.1 vs. 5.9 +/- 0.1 microM mL-1 in exercise and control groups, respectively; P < 0.01). Stimulation indices both by concanavalin A (Con A) and phytohaemagglutinin were also significantly higher in the exercise group (P < 0.01). A significant increase in the splenocyte production of interleukin-2 (IL-2) stimulated by Con A was noticed in the exercise group (354.1 +/- 28.8 vs. 218.9 +/- 23.5 pg mL-1 in exercise and control groups, respectively; P < 0.01). These findings suggest that voluntary exercise enhances not only macrophage function but also lymphocyte responsiveness in mice. In the studies of voluntary exercise, evaluation of NO2- production, as an indicator of macrophage function, is recommended.
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PMID:Immunomodulation by 8-week voluntary exercise in mice. 1071 79

The phosphoglucomutase (PGM)-encoding gene of Bordetella bronchiseptica is required for lipopolysaccharide (LPS) biosynthesis. An insertion mutant of the wild-type B. bronchiseptica strain BB7865 which disrupted LPS biosynthesis was created and characterized (BB7865pgm). Genetic analysis of the mutated gene showed it shares high identity with PGM genes of various bacterial species and forms part of an operon which also encompasses the gene encoding phosphoglucose isomerase. Functional assays for PGM revealed that enzyme activity is expressed in both bvg-positive and bvg-negative strains of B. bronchiseptica and is substantially reduced in BB7865pgm. Complementation of the mutated PGM gene with that from BB7865 restored the wild-type condition for all phenotypes tested. The ability of the mutant BB7865pgm to survive within J774. A1 cells was significantly reduced at 2 h (40% reduction) and 24 h (56% reduction) postinfection. BB7865pgm was also significantly attenuated in its ability to survive in vivo following intranasal infection of mice, being effectively cleared from the lungs within 4 days, whereas the wild-type strain persisted at least 35 days. The activities of superoxide dismutase, urease, and acid phosphatase were unaffected in the PGM-deficient strain. In contrast, the inability to produce wild-type LPS resulted in a reduced bacterial resistance to oxidative stress and a higher susceptibility to the antimicrobial peptide cecropin P.
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PMID:Role of phosphoglucomutase of Bordetella bronchiseptica in lipopolysaccharide biosynthesis and virulence. 1089 72

A Citrobacter sp. accumulated uranyl ion (UO2(2+)) via precipitation with phosphate ligand liberated by phosphatase activity. The onset and rate of uranyl phosphate deposition were promoted by NH4(+), forming NH(4)UO(2)PO(4), which has a lower solubility product than NaUO(2)PO(4). This acceleration decoupled the rate-limiting chemical crystallization process from the biochemical phosphate ligand generation. This provided a novel approach to monitor the cell-surface-associated changes using atomic-force microscopy in conjunction with transmission electron microscopy and electron-probe X-ray microanalysis, to visualize deposition of uranyl phosphate at the cell surface. Analysis of extracted surface materials by (31)P NMR spectroscopy showed phosphorus resonances at chemical shifts of 0.3 and 2.0 p.p.m., consistent with monophosphate groups of the lipid A backbone of the lipopolysaccharide (LPS). Addition of fUO2(2+) to the extract gave a yellow precipitate which contained uranyl phosphate, while addition of Cd(2+) gave a chemical shift of both resonances to a single new resonance at 3 p.p.m. Acid-phosphatase-mediated crystal growth exocellularly was suggested by the presence of acid phosphatase, localized by immunogold labelling, on the outer membrane and on material exuded from the cells. Metal deposition is proposed to occur via an initial nucleation with phosphate groups localized within the LPS, shown by other workers to be produced exocellularly in association with phosphatase. The crystals are further consolidated with additional, enzymically generated phosphate in close juxtaposition, giving high loads of LPS-bound uranyl phosphate without loss of activity and distinguishing this from simple biosorption, or periplasmic or cellular metal accumulation mechanisms. Accumulation of 'tethered' metal phosphate within the LPS is suggested to prevent fouling of the cell surface by the accumulated precipitate and localization of phosphatase exocellularly is consistent with its possible functions in homeostatis and metal resistance.
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PMID:Enzymically mediated bioprecipitation of uranium by a Citrobacter sp. : a concerted role for exocellular lipopolysaccharide and associated phosphatase in biomineral formation. 1093 90

Three distinct sub-populations of macrophages derived from goldfish kidney leukocyte cultures were generated and characterised. The sub-populations designated as R1, R2 and R3-type macrophages had distinct morphological, cytochemical and flow cytometric profiles, and also differed in their anti-microbial functions after activation with macrophage activation factors (MAF) and bacterial lipopolysaccharide (LPS). The R1-type macrophages were small cells that contained acid phosphatase, but lacked myeloperoxidase and non-specific esterase. The R2-type macrophages were morphologically similar to mature tissue macrophages of mammals, and were positive for acid phosphatase, myeloperoxidase and non-specific esterase. The R3-type macrophages were round cells with eccentrically placed nuclei and resembled mammalian monocytes. This sub-population stained for acid phosphatase, myeloperoxidase and non-specific esterase. The R2 and R3-type macrophages exhibited distinct functional responses after activation with MAF and/or LPS. R2-type macrophages were potent producers of nitric oxide, while R3-type macrophages produced little or no nitric oxide after activation with MAF and LPS. The R2 and R3-type macrophages also exhibited unique respiratory burst responses (ROI) after treatment with MAF and/or LPS. After treatment with MAF and LPS, activated R2 macrophages were primed for ROI after only 6 h of stimulation with the activating agents, and continued to exhibit a strong ROI response for an extended cultivation period (48 h). In contrast, activated R3-type macrophages showed an early ROI response (6 h after treatment with MAF and LPS), which decreased significantly by 48 h after treatment with the activating agents. Our results suggest that the analysis of the mechanisms of induction of fish anti-microbial responses may be dependent upon the concerted actions of functionally distinct macrophage sub-populations.
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PMID:Generation and functional analysis of distinct macrophage sub-populations from goldfish (Carassius auratus L.) kidney leukocyte cultures. 1093 19

Tartrate-resistant acid phosphatase (TRAP) is a lysosomal di-iron protein of mononuclear phagocytes and osteoclasts. Hitherto, no role for the enzyme in immunity has been identified; however, knockout mice lacking TRAP have a skeletal phenotype caused by an intrinsic osteoclast defect. To investigate a putative function for TRAP in macrophages (Mphi), we investigated proinflammatory responses and systemic microbial clearance in knockout mice compared with age- and gender-matched congenic wild-type mice. Phorbol 12-myristate 13-acetate (PMA)-stimulated and interferon-gamma (IFN-gamma)-induced superoxide formation was enhanced in peritoneal Mphi lacking TRAP; nitrite production in response to stimulation with lipopolysaccharide (LPS) and IFN-gamma was also increased. In addition, secretion of the proinflammatory cytokines, tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-12, was significantly greater in TRAP-deficient Mphi when stimulated with LPS, with or without addition of either TNF-alpha or IFN-gamma. The activity of tartrate-sensitive (lysosomal) acid phosphatase was increased in Mphi from the knockout mice but activities of the lysosomal hydrolases N-acetyl beta-glucosaminidase and acid beta-glucuronidase were unchanged, indicating selective activation of compensatory acid phosphatase activity. Evidence of impaired Mphi function in vivo was obtained in TRAP knockout mice, which showed delayed clearance of the microbial pathogen, Staphylococcus aureus, after sublethal intraperitoneal inoculation. After microbial challenge, peritoneal exudates obtained from TRAP knockout mice had a reduced population of Mphi. As peritoneal Mphi and neutrophils lacking TRAP were able to phagocytose and kill S. aureus normally in vitro, TRAP may directly or indirectly influence recruitment of Mphi to sites of microbial invasion. Our study shows that TRAP participates in the inflammatory response of the Mphi and influences effector signalling pathways in innate immunity.
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PMID:Mice lacking tartrate-resistant acid phosphatase (Acp 5) have disordered macrophage inflammatory responses and reduced clearance of the pathogen, Staphylococcus aureus. 1116 43

The purpose of this investigation was to determine the effects of bon narine treatment on macrophage and lymphocyte functions in mice. Twelve week-old female inbred BALB/c mice were given bon narine p.o. at 30 mg/kg per day and sacrificed after three months. Glucose consumption of peritoneal macrophages in the bon narine treated group during incubation up to 72 h was significantly higher than that in the control group. Activities of acid phosphatase (APH), beta-glucuronidase (GLU) and lactate dehydrogenase (LDH) in the peritoneal macrophages in the bon narine treated group significantly increased compared to that in the control group. Macrophage production of nitric oxide stimulated by lipopolysaccharide (LPS) in the bon narine treated group was significantly increased. Interleukin-1beta (IL-1beta) production of peritoneal macrophages stimulated by LPS was significantly higher in the bon narine treated group. Stimulation indices in splenic lymphocytes by concanavalin A (Con A) in the bon narine treated group were significantly higher than that in the control group. Interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) production stimulated by Con A were significantly increased in the bon narine treated mice. Interleukin-4 (IL-4) production of splenic lymphocytes stimulated by Con A was not different in the control group and the bon narine treated group. These findings might suggest that oral administration of bon narine effectively enhanced the macrophage function and lymphocyte responsiveness in mice.
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PMID:Enhanced macrophage functions and cytokine production of lymphocytes after ingestion of bon narine in female BALB/c mice. 1119 48

With future exploration of macrophage properties in mind, we established a novel cell line (HS-P) from a transplantable histiocytic sarcoma, derived originally from a tumour in an aged F344 rat. HS-P was subjected to 70 serial passages, in which the mean doubling time was 15.7 h. The cells, which were round, oval or polygonal in shape, were arranged in a compact sheet. They reacted to varying degrees for lysosomal enzymes (acid phosphatase and non-specific esterase) and with the following antibodies: ED1/ED2 (rat macrophage/histiocyte-specific), OX6 (rat MHC class II-specific), lysozyme antibody and alpha1-antichymotrypsin antibody. Electron microscopically, HS-P cells showed lysosomes and prominent cell projections. These findings indicated that the cultured cells were macrophage-like. Syngeneic rats inoculated subcutaneously or intraperitoneally with HS-P cells invariably developed sarcomatous tumours consisting of monomorphic mononuclear cells, which exhibited cytochemical properties similar to those of cultured HS-P cells. Bioassay and reverse transcription-polymerase chain reaction methods revealed that tumour necrosis factor-alpha increased on addition of lipopolysaccharide (LPS), indicating that HS-P cells remained LPS-responsive. HS-P cells may prove to be a useful tool for in-vitro studies of macrophage function.
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PMID:Macrophage-like cell line (HS-P) from a rat histiocytic sarcoma. 1122 16


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