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

Neutrophil-specific granule deficiency (SGD) is a rare, congenital disease characterized by atypical neutrophil structure and function, resulting in recurrent bacterial infections from early infancy. Homozygous recessive mutations in the CCAAT/enhancer-binding protein epsilon (C/EBPepsilon) gene were described in two of five SGD patients, indicating loss of C/EBPepsilon function as the primary genetic defect in this disease. C/EBPepsilon is expressed in murine and human macrophages. Macrophages from the C/EBPepsilon-deficient mice show impaired differentiation, phagocytic activity, and transcription of macrophage-specific genes. To determine if monocyte/macrophage cells are impacted in SGD, we analyzed phenotypic features of peripheral blood (PB) monocytes in a SGD individual lacking functional C/EBPepsilon. Flow cytometric analysis of PB leukocytes revealed aberrant expression of CD45, CD11b, CD14, CD15, and CD16 on cells from the SGD individual. Also, the PB CD14(+) cells from this individual, weakly stained for the monocyte-specific enzyme, nonspecific esterase, and electron microscopic examination, indicated morphologic differences between the SGD cells and those from normal controls. Serum interleukin (IL)-6 levels in the SGD individual during a severe bacterial infection were lower compared with levels in other non-SGD individuals with sepsis. In contrast, serum IL-8 levels were markedly elevated in the SGD individual compared with those of non-SGD individuals in sepsis. PB CD14(+) cells from the SGD individual expressed higher IL-8 mRNA levels compared with normal controls in response to lipopolysaccharide and interferon-gamma. These phenotypic and functional alterations of PB monocytes in the SGD individual suggest that C/EBPepsilon plays a critical role in monocyte/macrophage development of humans and is consistent with observations in the murine system. This study implicates abnormalities in monocytes/macrophages and neutrophils in the onset and development of SGD.
 ...
PMID:Phenotypic and functional alterations of peripheral blood monocytes in neutrophil-specific granule deficiency. 1457 62

Pseudomonas aeruginosa is a model for studying opportunistic pathogens that are highly resistant to most classes of antibiotics and cause chronic pulmonary infections. We have developed and adapted a multiplex polymerase chain reaction-based signature-tagged mutagenesis (STM) for high-throughput screening of a collection of 7968 P. aeruginosa mutants in a rat model of chronic respiratory infection. After three rounds of screening, a total of 214 mutants, representing transposition events into 148 open reading frames, were shown to be attenuated in lung infection and were retained for further analysis. As proof of concept supporting this technology, we identified 11 insertions in typical virulence genes such as those coding for pili implicated in motility, attachment and swarming, alginate synthesis and its expression, a mucus transcription regulator, extracellular enzymes such as alkaline protease, esterase and amino peptidase, a rhamnosyl surfactant transferase and a lipopolysaccharide glycosyl transferase. Detailed analysis of the 148 STM mutants, including seven auxotrophs, revealed insertions in 21 of the 26 known gene classes used to characterize sequenced bacterial genomes. We noted that at least 46% of STM mutants identified had insertions in hypothetical proteins or proteins of unknown function and that approximately 40% of all STM mutants had insertions in surface proteins including the outer membrane, the periplasm and the inner membrane. Interestingly, 11 STM mutants attenuated for lung infection were also identified in microarray and transcriptome for quorum sensing and mucoidy production. The remaining 130 mutants were systematically analysed for their capability to express fully known virulence factors. In addition, testing the ability of these mutants to infect alternative model host Drosophila melanogaster revealed 36 STM mutants defective in protease, twitching motility, swimming and swarming. Finally, we identified many genes, the activity of which in respiratory infection was not fully appreciated.
 ...
PMID:In vivo functional genomics of Pseudomonas aeruginosa for high-throughput screening of new virulence factors and antibacterial targets. 1464 75

The locomotor responses of human peripheral blood neutrophils and lymphocytes were measured by the change from spherical to polarized shapes in the presence of endotoxins (lipopolysaccharide, LPS) of enteric pathogens: S. dysenteriae type 1, V. cholerae Inaba 569B, S. typhimurium, and K. pneumoniae. We reported earlier that these endotoxins are chemotactic factors for the neutrophils since they stimulated cell polarization within a few minutes of incubation. Endotoxins had an inhibitory effect upon neutrophil phagocytosis of opsonized yeast and the cells engulfed fewer yeasts. Interestingly, endotoxins increased neutrophil adhesion to clean glass surfaces, but stimulated the cells to exhibit increased random locomotion (chemokinesis) through cellulose nitrate filters and show an enhanced ability to reduce nitroblue tetrazolium (NBT) dye. Unlike neutrophils, lymphocytes direct from blood do not show polarized morphology towards chemotactic factors but the cells acquire locomotor capacity during 24-72 h culture with mitogens such as phytohemagglutinin (PHA), phorbol myristate acetate or concanavalin A. Stimulation of blood lymphocytes with endotoxins did not induce cell polarization in short-term but long-term culture resulted in an increase in the proportion of polarized cells that acquired locomotor morphologies. The majority of these cells were identified as esterase negative B-lymphocytes that migrated through filters. Despite the optimum time of incubation for each of these cell types being different, we found that lymphocytes respond to much lower concentrations of endotoxins than the neutrophils. These findings suggest that endotoxins of enteric pathogens modulate the functions of human blood neutrophils and lymphocytes.
 ...
PMID:Endotoxins of enteric pathogens modulate the functions of human neutrophils and lymphocytes. 1465 75

In our ongoing efforts to develop new methods for lipopolysaccharide (LPS) detoxification, we have screened lipase/esterase libraries for the ability to deacylate the 2'- and 3'-fatty acid chains from lipid A: the most active esterases were successfully employed to inactivate LPSs in a crude concentrated cell supernatant of E. Coli containing a recombinant single chain antibody (scFv).
 ...
PMID:Probing lipase/esterase libraries for lipid A hydrolases--discovery of biocatalysts for the detoxification of bacterially-expressed recombinant protein. 1476 10

The effect of separate and combined 10-day treatment with phenobarbital (PB) in a single daily dose of 35 mg/kg and E. coli lipopolysaccharide (LPS) in a dose of 25 microg/kg was studied in white rats. The results were evaluated by the rate of DNA synthesis in the culture of T mitogen stimulated thymocytes, the activity of glucose-6-phosphate dehydrogenase (G-6-PDG) in the thymus, and the activity of acetylcholine esterase (ACE) and the content of catecholamines (CA) in the nerve fibers of this organ. It was established that the 10-day treatment with PB inhibits the proliferative activity in concanavalin A stimulated lymphocytes of rat thymus, decreases the ACE activity, and increases the CA content in the nerve fibers. The repeated injections of E. coli LPS on the background of PB led to more pronounced negative changes in the functional activity of lymphoid cells in the thymus, manifested by a decrease in the G-6-PDG activity and the rate of DNA synthesis in the thymus and by an increase in the level of biogenic amines in the nervous fibers of this organ.
 ...
PMID:[The functional state of thymus cells under prolonged combined action of phenobarbital and E. coli lipopolysaccharide]. 1534 Oct 71

The in vitro generation of dendritic cells (DCs) from either blood or bone marrow has been accomplished for humans and a number of other species. This ability has facilitated the opportunity to test the efficacy of DC vaccines in various tumor models. The cottontail rabbit papillomavirus (CRPV) model is the most clinically relevant animal model for human papillomavirus (HPV)-associated carcinogenesis. The CRPV model has been used to test various preventative and therapeutic vaccination strategies, and the availability of rabbit DCs would further expand its utility. However, to date, rabbit DCs have not been phenotypically and/or functionally characterized. Here we show that DCs can be generated in vitro from rabbit bone marrow mononuclear cells (BMMCs) cultured in the presence of the human cytokines GM-CSF and IL-4 and matured with lipopolysaccharide (LPS). These cells show upregulation of MHC class II and CD86, as well as downregulation of CD14, do not have non-specific esterase activity, are able to perform receptor-mediated endocytosis, and are potent stimulators of allogeneic T cell proliferation in mixed lymphocyte reactions. The ability to generate rabbit DCs makes it possible to test the efficacy of DC vaccination in the prevention and treatment of CRPV-induced lesions, which may provide useful preclinical data regarding the use of DC vaccines for HPV-associated lesions, including cervical cancer.
 ...
PMID:Generation of dendritic cells from rabbit bone marrow mononuclear cell cultures supplemented with hGM-CSF and hIL-4. 1562 3

We present reference maps of the mouse serum proteome (run under reducing and non-reducing conditions), from control animals, from mice injected with lipopolysaccharide (LPS) to induce systemic inflammation, and from mice transgenic for human apolipoproteins A-I and A-II. Seventy-seven spots/spot chains from the reducing gels were identified by HPLC MS/MS, representing 28 distinct proteins, including a species-specific protease inhibitor, contrapsin, and high levels of carboxylesterase. The concentrations of acute-phase reactants were monitored for 96 h after LPS challenge. The greatest changes (four-fold 48 h after LPS administration) were observed for haptoglobin and hemopexin. Orosomucoid/alpha(1)-acid glycoprotein and apolipoprotein A-I increased steadily, to 50-60% above baseline at 96 h from stimulation. In mice transgenic for human apolipoprotein A-I the levels of expression of orosomucoid/alpha(1)-acid glycoprotein, alpha(1)-macroglobulin, esterase, kininogen and contrapsin were altered compared to knockout mice lacking apolipoprotein A-I. In contrast, except for the presence of apolipoprotein A-II, no statistically significant difference was observed in mice transgenic for human apolipoprotein A-II.
 ...
PMID:Reference maps of mouse serum acute-phase proteins: changes with LPS-induced inflammation and apolipoprotein A-I and A-II transgenes. 1619 95

Silver nitrate administration stimulates immune activation, inflammation and deterioration in cell function. It is well established that hippocampal and cortical tissue are susceptible to degeneration in responses to insult such as oxidative stress or infection. This study was designed to investigate the prophylactic effect of alpha-crystallin, a major chaperone lens protein comprising of alpha-A and alpha-B subunits in inflammation induced mice. Mice were divided into three groups (n=6 in each), control, inflammation and alpha-crystallin treated. Our result shows that alpha-crystallin pretreatment effectively diminished systemic inflammation induced glial fibrillary acidic protein (GFAP) and nuclear factor kappa B (NFkappaB) expression in the mice neocortex, reversed elevated intracellular calcium levels, acetylcholine esterase activity and depletion of glucose. Furthermore it also significantly prevented nitric oxide (P<0.05) and lipid peroxide production in the plasma, liver, neocortex and hippocampus of the inflammation-induced mice. In order to demonstrate the direct *OH and nitric oxide radical scavenging ability of alpha-crystallin, an In vitro experiment using primary astrocyte culture subjected to lipopolysaccharide (LPS), a well-known inflammatory stimuli were also carried out. This study reiterates that alpha-crystallin therapy may serve as a potent pharmacological agent in neuroinflammation.
 ...
PMID:Molecular chaperone alpha-crystallin prevents detrimental effects of neuroinflammation. 1644 50

We have developed a cell-based model of thrombin generation using activated monocytes as a source of tissue factor (TF) and platelets serving as a surface for thrombin generation. Monocytes are activated by lipopolysaccharide and express cell-bound TF. To these are added physiologic (plasma) concentrations of all the plasma procoagulants as well as TF pathway inhibitor, antithrombin, and C1-esterase inhibitor. Coagulation takes place in microtiter wells and is initiated by factor VIIa (FVIIa) and calcium. At time intervals, aliquots are removed, platelet activation is measured by the expression of P-selectin, and thrombin generation is measured by chromogenic assay. In addition, one can measure the activation of FIX, FX, FVIII, FV, and FXI. Initial results reveal that the FVIIa-TF interaction results in the activation of FX to FXa and FIX to FIXa. FXa stays in the vicinity of the TF-bearing cell and, in the presence of FVa, converts a small amount of prothrombin to thrombin on the surface of the TF cell. This small amount of thrombin is not sufficient to clot fibrinogen, but is sufficient to activate platelets and FVIII, FV, and FXI. Following platelet activation, FVIIIa, FVa, and FXa occupy sites on the activated platelet surface. FIXa, activated by TF-FVIIa, does not remain on the TF cell, but converts FX to FXa on the platelet surface. FXIa acts to boost FIXa generation on the activated platelet, increasing FXa and subsequent thrombin generation. We have also shown that activated protein C does not inactivate Va on the platelet surface but rather on endothelial cell surfaces.
 ...
PMID:A cell-based model of thrombin generation. 1667 64

Effector cells of the innate immune system have diverse functions that can result in tumour inhibition or tumour progression. Activation of macrophages by CD40 ligation has been shown to induce antitumour effects in vitro and in vivo. Here we investigated the role of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha) as mediators in the tumoristatic effects of murine peritoneal macrophages activated with agonistic anti-CD40 monoclonal antibody (alphaCD40) alone and following further stimulation with bacterial lipopolysaccharide (LPS). We found that macrophages activated in vivo by alphaCD40 exhibited tumoristatic activity in vitro against B16 melanoma cells; the tumoristatic effect correlated with the level of NO production and was enhanced by LPS. Use of the NO inhibitor L-nitro-arginine-methyl esterase (L-NAME) and evaluation of macrophages from inducible NO synthase (iNOS)-knockout (KO) mice following alphaCD40 activation showed reduced tumoristatic activity. CD40 ligation enhanced expression of TNF-alpha. Macrophage tumoristatic activity following alphaCD40 treatment was reduced by TNF-alpha mAb or use of macrophages from TNF-alpha-KO mice. However, further stimulation of alphaCD40-activated macrophages with LPS resulted in strong tumoristatic activity that was much less dependent on NO or TNF-alpha. Taken together, these results suggest that NO and TNF-alpha are involved in, but not solely responsible for, the antitumour effects of macrophages after activation by CD40 ligation.
 ...
PMID:Tumoristatic effects of anti-CD40 mAb-activated macrophages involve nitric oxide and tumour necrosis factor-alpha. 1677 62


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>