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)

A temperate phage, designated Sf6, has been isolated from Shigella flexneri 3a. Characterization of Sf6 revealed that it possesses the capacity for converting the S. flexneri 3,4 group antigen complex to group factor 6. Serological studies and chemical analysis of lipopolysaccharide from converted strains suggest that group factor 6 is a reflection of an acetylation of the preexisting 3,4 antigen complex. Evidence is provided that the 3,4 group antigen complex functions, at least in part, as a cell surface receptor site for Sf6 adsorption.
 ...
PMID:Phage conversion of Shigella flexneri group antigens. 109 48

Thrombomodulin (TM), the endothelial cell surface receptor for thrombin-mediated activation of protein C and of its anticoagulant system, is involved in maintaining vascular nonthrombogenicity, and depressed TM activity may induce intravascular fibrin formation. TM antigen was previously found by immunohistochemical methods in rabbit glomeruli. We therefore attempted to identify the corresponding TM activity in isolated detergent-solubilized rat and human glomeruli. Like purified lung TM, rat glomeruli extracts accelerated the hydrolysis by activated protein C of the chromogenic substrate S-2238 in the presence of 10 nM thrombin, as determined by spectrophotometry. One mg glomerular protein promoted the formation of 681 +/- 115 nmol activated protein C, the equivalent of the amount generated by 845 ng of purified rabbit TM. TM activity correlated with the protein content of the glomerular extracts (r = 0.94). These extracts prolonged rat plasma activated partial thromboplastin time. Incubation of glomeruli with tumor necrosis factor-alpha (TNF) or E. coli lipopolysaccharide depressed their TM-like activity in a dose and time dependent manner. Incubation with TNF suppressed their anticoagulant activity. In human glomeruli, TM activity was also found at a level which corresponded to their TM antigen content, and was determined by ELISA with mouse monoclonal antibody. These results indicate that measurement of glomerular TM activity might help to clarify the mechanisms of intraglomerular fibrin deposition in renal diseases.
 ...
PMID:Quantification and modulation of thrombomodulin activity in isolated rat and human glomeruli. 131 19

The migration of peritoneal cells from 25 continuous ambulatory peritoneal dialysis patients and eight healthy women undergoing laparoscopy were studied. Peritoneal cells of continuous ambulatory peritoneal dialysis patients migrated to commonly used chemoattractants, like N-formyl-methionyl-leucyl-phenyl-alanine-methyl- ester and casein, but they also migrated to high concentrations of recombinant interleukin-1 alpha and to endotoxin (lipopolysaccharide). In the peritoneal effluent from continuous ambulatory peritoneal dialysis patients a rather heat stable chemoattractant was found with a molecular weight of 40-200 kDa with an optimal activity at approximately 125 kDa. The chemoattractant is a protein and is not complement factor 5a or interleukin-1 and was only found in peritoneal effluent from continuous ambulatory peritoneal dialysis patients, but not in peritoneal fluid from healthy women undergoing laparoscopy. Therefore, peritoneal dialysis might induce the generation of a chemoattractant. The optimal chemotactic response of peritoneal cells from continuous ambulatory peritoneal dialysis patients to N-formyl-methionyl-leucyl-phenyl-alanine-methyl- ester in medium could be enhanced by replacing the medium by peritoneal effluent. So the chemotaxis of peritoneal cells to the factor in the peritoneal effluent is caused by another mechanism, which might involve different cell surface receptor populations, than the chemotactic response to N-formyl-methionyl-leucyl-phenyl-alanine-methyl-ester.
 ...
PMID:Chemotaxis of the peritoneal cells and the detection of a chemo-attractant in the effluent from peritoneal dialysis patients. 212 88

The type 3 complement receptor (CR3), initially identified as the leukocyte cell surface receptor for iC3b, is now known to form part of the extended integrin family of cell adhesion molecules that mediate both cell-cell and cell-extracellular matrix interactions. The identification of a heritable deficiency of human leukocyte adhesion together with the advent of monoclonal antibodies has shed some light on the central role of CR3 in the transendothelial migration of macrophages and neutrophils to sites of inflammation. We review the general structural features of CR3 and then examine our understanding of its role in both nonspecific and T cell-dependent inflammatory processes based on our murine in vivo experiments. CR3-dependent inflammation seems to contribute to the pulmonary response to some stimuli (lipopolysaccharide) but not to others (bacillus Calmette-Guerin). These studies highlight the potential therapeutic benefits, as well as the significant risks of potentiating acute bacterial infections, of CR3 blockade in vivo.
 ...
PMID:The role of the type 3 complement receptor in the induced recruitment of myelomonocytic cells to inflammatory sites in the mouse. 214 91

These studies were designed to test the hypothesis that changes in intracellular Ca2+ levels and activation of the calcium ion- and phospholipid-dependent protein kinase C were required for the induction of macrophage tumoricidal activity by interferon-gamma (IFN-gamma). Phenothiazines and R24571, known antagonists of calcium-binding proteins and therefore nonspecific inhibitors of protein kinase C, blocked in a dose-dependent manner the induction of macrophage cytocidal activity by either natural or recombinant IFN-gamma. Macrophages depleted of intracellular Ca2+ by chelation with Quin 2, were also unresponsive to IFN-gamma. These treatments effected neither the binding of IFN-gamma to its cell surface receptor nor the normal intracellular processing of IFN-gamma. Activators of protein kinase C (such as phorbol esters) and Ca2+ ionophores when added alone did not effect the activation state of the macrophage population. However, macrophages exposed to both drugs in combination were elevated into the primed activation state such that in the presence of a second signal (lipopolysaccharide or heat killed Listeria monocytogenes), the cells were triggered to express full levels of tumoricidal activity. The capacity of phorbol esters to induce cellular activation correlated with their ability to bind and to activate protein kinase C. No synergistic effect was observed between IFN-gamma and protein kinase C activators and/or Ca2+ ionophores, indicating that the drugs could only prime and could not trigger macrophages for tumor cell killing. These results thus support the concept that protein kinase C activation and mobilization of intracellular Ca2+ are essential steps in the pathway of IFN-gamma-dependent induction of non-specific tumoricidal activity in macrophages.
 ...
PMID:Role of protein kinase C and intracellular calcium mobilization in the induction of macrophage tumoricidal activity by interferon-gamma. 309 74

A rat monoclonal antibody (NIM-R3) was found to be reactive with activated mouse B cells but neither activated T cells nor small resting lymphocytes, T or B. The antibody stains antibody-forming cell precursors within 48 hr of primary or secondary immunization in vivo, but not at longer times (greater than 14 days) immunization. When added to cultures of spleen cells responding in vitro to dinitrophenylated bovine, IgG, the number of antibody-forming cells was increased. NIM-R3 also maintained the proliferation of purified B blasts in the absence of lipopolysaccharide, but did not activate small resting B cells in the presence of anti-Ig. NIM-R3 could replace B-cell growth factor (BCGF II) in cultures of the murine B-cell lymphoma BCL1 inducing proliferation but not differentiation. Finally, competition was demonstrated for binding sites on BCL1 cells between BCGF II and NIM-R3, but not between NIM-R3 and T-cell replacing factor (B15-TRF). We suggest that NIM-R3 may represent a novel specificity and may be directed against the cell surface receptor for BCGF II, and in turn this receptor may be independent of the B15-TRF and BSF1 receptors.
 ...
PMID:Monoclonal antibody NIM-R3 substitutes for B-cell growth factor. 348 71

CD14 is a 55-kD protein found as a glycosylphosphatidylinositol (GPI)-anchored protein on the surface of monocytes, macrophages, and polymorphonuclear leukocytes, and as a soluble protein in the blood. Both forms of CD14 participate in the serum-dependent responses of cells to bacterial lipopolysaccharide (LPS). While CD14 has been described as a receptor for complexes of LPS with LPS-binding protein (LBP), there has been no direct evidence showing whether a ternary complex of LPS, LBP, and CD14 is formed, or whether CD14 binds LPS directly. Using nondenaturing polyacrylamide gel electrophoresis (native PAGE), we show that recombinant soluble CD14 (rsCD14) binds LPS in the absence of LBP or other proteins. Binding of LPS to CD14 is stable and of low stoichiometry (one or two molecules of LPS per rsCD14). Recombinant LBP (rLBP) does not form detectable ternary complexes with rsCD14 and LPS, but it does accelerate the binding of LPS to rsCD14. rLBP facilitates the interaction of LPS with rsCD14 at substoichiometric concentrations, suggesting that LBP functions catalytically, as a lipid transfer protein. Complexes of LPS and rsCD14 formed in the absence of LBP or other serum proteins strongly stimulate integrin function on PMN and expression of E-selectin on endothelial cells, demonstrating that LBP is not necessary for CD14-dependent stimulation of cells. These results suggest that CD14 acts as a soluble and cell surface receptor for LPS, and that LBP may function primarily to accelerate the binding of LPS to CD14.
 ...
PMID:Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14. 750

Extravasation of leukocytes at sites of ischemia may mediate tissue injury. To determine how leukocyte accumulation may be induced by ischemia, effects of hypoxia on basal neutrophil expression of adhesion and activation receptors were examined. Effects of hypoxia upon preactivated cells were also studied. To determine whether regulation of expression is dependent on oxygen availability or on mitochondrial respiration, the effects of physical hypoxia (substitution of O2 by nitrogen) were compared with those of chemical hypoxia with sodium cyanide (NaCN). Leukocytes in whole blood (eight volunteers) were exposed either to hypoxia alone or to priming concentrations of lipopolysaccharide (LPS, 1 microgram/ml) followed by chemical hypoxia (NaCN, 1 mM) or physical hypoxia (PO2 of 1-10 torr) for various time intervals. Room air was controlled and hypoxic cells were labeled with fluorescent monoclonal antibodies to integrins CD18 and CD11b or to the 55-kDa TNF alpha cell surface receptor (TNFR). Receptor concentrations were measured by flow cytometry. Data were analyzed by ANOVA/Student's t test. Physical hypoxia increased expression of both CD11b and CD18 over time and augmented their LPS-induced up-regulation. Isolated chemical hypoxia did not change neutrophil expression of CD11b or CD18, but partially inhibited neutrophil CD11b and CD18 up-regulation by LPS. LPS-induced TNFR down-regulation was not affected by physical hypoxia, which failed to alter TNFR expression in this model.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Hypoxia-induced alterations of neutrophil membrane receptors. 763 Jan 18

The met proto-oncogene encodes the cell surface receptor for hepatocyte growth factor (HGF) and transmits its multifunctional signals such as regulation of cell proliferation, motility, and morphogenesis. These pleiotropic actions attributable to HGF are mainly reported on cells of epithelial derivation which express the Met receptor. The HGF gene, on the other hand, is expressed in mesenchymally derived cells including peripheral blood leukocytes. Recently, we reported that Met receptor gene expression in epithelial cells is induced by inflammatory cytokines; currently, however, little is known concerning Met gene expression in mesenchymal cells. In the present study, we have explored the role of Met expression during monocyte-macrophage differentiation using THP-1 cells, a monocytic cell line, and monocytes freshly isolated from normal human peripheral blood. We have found that untreated monocytes do not express Met mRNA and protein. Upon incubation with differentiation inducers such as 12-O-tetradecanoylphorbol-13-acetate, lipopolysaccharide, a combination of interleukin (IL) 6 plus tumor necrosis factor (TNF) alpha, or IFN-gamma plus TNF-alpha, a pronounced increase in the amounts of Met mRNA and protein are seen in THP-1 cells. The expression of Met appears to correlate with the onset of differentiation of monocytes as noted by changes in cell morphology and adherence to culture plates, and the increased accumulation of Met protein was observed only in cells that differentiated and adhered to the culture dish. Moreover, Met was found to be phosphorylated on tyrosine residues, indicating that the receptor is potentially involved in signal transduction events. Addition of exogenous HGF to the activated cells resulted in the suppression of cell proliferation and an increase in cell motility. Reverse transcription-PCR and Western blot analyses revealed that untreated THP-1 cells contain HGF transcript and protein, and that HGF expression is inducible by addition of the differentiation agents such as 12-O-tetradecanoylphorbol-13 acetate or IL-6 plus TNF-alpha. Immune serum that is specific for neutralizing HGF activity markedly inhibited monocyte differentiation (50% reduction in cell attachment and process formation) induced by IL-6 and TNF-alpha. Moreover, we also found that the mRNA for Ron, which encodes a tyrosine kinase receptor for HGF-like protein (also known as macrophage-stimulating protein), is induced in THP-1 cells during the course of their differentiation to macrophages by IFN-gamma plus TNF-alpha. These findings indicate that the HGF and Met families may indeed be physiological regulators of monocyte-macrophage differentiation/maturation.
 ...
PMID:Induction of met proto-oncogene (hepatocyte growth factor receptor) expression during human monocyte-macrophage differentiation. 878 Aug 95

Influenza A viruses display T cell-independent polyclonal B cell-activating properties which are mediated by the B cell-superstimulatory envelope glycoprotein hemagglutinin (HA). In this report, the receptor-binding requirements for B cell activation by influenza viruses were expected. Neuraminidase treatment of resting mature B cells from BALB/c mice abrogated late (proliferation/immunoglobulin synthesis), early (up-regulation of cell surface markers, including CD25, B220, and B7-1) and very-early events (homotypic adhesion) in virus-responding B lymphocytes. Similarly, pretreatment of murine responder cells with different inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin) significantly suppressed subsequent B lymphocyte activation by HA, but not control responses to lipopolysaccharide or anti-mu. Assays with chimeric HA transfectants, expressing the loop region of epitope B (amino acids 155-160) of the globular head of H2 (high B cell-stimulatory subtype) or H3 (medium-stimulatory subtype) on the protein backbone of a low-stimulatory subtype (H1) failed to alter the B cell-stimulatory activity of the virus, suggesting that the hypervariable loop region is not crucial in determining the B cell-activating properties of the protein. Collectively, our results imply that the B cell-superstimulatory function of influenza virus HA is not mediated by a direct protein/protein interaction, but via binding of HA to terminal sialic acid residues on cell surface receptor glycoproteins. These findings identify the influenza virus HA glycoprotein as the first viral lectin with lymphocyte-activating properties.
 ...
PMID:Influenza A virus hemagglutinin is a B cell-superstimulatory lectin. 881 51


1 2 3 4 5 6 Next >>