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)

The mechanism through which human blood platelets interact with gram-negative bacteria with well-defined structural variations in endotoxic lipopolysaccharide was studied. Secretion of 14C-serotonin and aggregation of platelets separated from plasma proteins were observed on challenge with rough mutant Re595 of Salmonella minnesota possessing a glycolipid outer layer composed of Lipid A and 2-keto-3-deoxyoctonate (KDO) but lacking heptose phosphate in the core and O-polysaccharide in its outer portion. Both 14C-serotonin secretion and platelet aggregation were concentration-dependent, with a half-maximum response at the ratio of one bacterial colony-forming unit (CFU) to two platelets. The aggregation of human platelets induced by mutant Re595 was divalent cation-dependent and required secretion of ADP and fibrinogen from platelet storage granules because it was inhibited by chelators, by the ADP-splitting enzyme apyrase, and by monospecific antifibrinogen Fab fragments. The synthetic peptide analog of the platelet receptor recognition site on the gamma chain of fibrinogen, gamma 400-411, inhibited platelet aggregation induced by mutant Re595 (IC50 160 mumol/L), whereas serotonin secretion was unaffected. Tetrapeptide, RGDS, analogous to human fibrinogen alpha chain (alpha 572-575) and to the cell adhesion site of fibronectin, also inhibited aggregation induced by mutant Re595 (IC50 60 mumol/L). Secretion of 14C-serotonin was preceded by a very rapid phosphorylation of a platelet protein of mol wt 47,000, which is associated with protein kinase C activation. Myosin light chain (mol wt 20,000) was also phosphorylated. Both phosphoproteins were dephosphorylated while secretion was reaching maximum. Furthermore, release of 3H-arachidonic acid from platelet phospholipids and generation of thromboxane B2 via the cyclooxygenase pathway were observed. Inhibition of this pathway with acetylsalicylic acid (10(-4) mol/L) or indomethacin (5 X 10(-4) mol/L) reduced 14C-serotonin secretion and platelet aggregation. The role of Lipid A in the interaction of mutant Re595 with human platelets was deduced from the inhibitory effect of the Lipid A-binding protein present in Limulus amebocyte lysate. Likewise, polymyxin B, known to complex with Lipid A, was inhibitory. The reactivity of mutant Re595 toward platelets was attenuated by mild acid hydrolysis, during which KDO was dissociated from the glycolipid, and by alkaline hydrolysis, which breaks ester-linked fatty acids in Lipid A. In contrast to mutant Re595, strain S218 of S minnesota bearing "complete" endotoxic lipopolysaccharide did not induce secretion and aggregation of human platelets.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanism of human platelet activation by endotoxic glycolipid-bearing mutant Re595 of Salmonella minnesota. 376 28

A variety of responses of cells of the lymphoid system are associated with acquisition of the capacity to initiate the coagulation protease pathways. The initiating or procoagulant molecules are produced by the monocyte; however, a number of studies have indicated that lymphocyte collaboration is required. The induction of human monocyte procoagulant activity (PCA) by the model stimulus bacterial lipopolysaccharide (LPS) was examined in the present study by using relatively highly purified monocyte and lymphocyte populations in reconstitution experiments. Consistent with prior studies, the PCA response could not be generated by highly purified monocytes alone after exposure to LPS. The ability to generate PCA was restored to these monocyte populations by the addition of fibronectin-gelatin nonadherent lymphocytes, nylon wool effluent T cells, or Leu-3a+ inducer/helper T cells selected by fluorescence-activated cell sorting. T cells added to monocytes at a ratio of 8:1 or higher, and Leu-3a+ cells added at a ratio of 6:1 or higher, provided a maximal collaboration for monocyte PCA induction by LPS. These results substantiate further previous suggestions of an absolute requirement for collaborating T cells and demonstrate that these instructor cells carry a marker for the inducer/helper subset.
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PMID:The instructor cell for the human procoagulant monocyte response to bacterial lipopolysaccharide is a Leu-3a+ T cell by fluorescence-activated cell sorting. 660 44

Purified rat plasma fibronectin (Fn) was studied for its ability to influence nonspecific lymphocyte transformation to various mitogens. Fn added to lymph node cells (LNC) stimulated with phytohemagglutinin (PHA), concanavalin A (Con A), or bacterial lipopolysaccharide (LPS) resulted in a noncytotoxic dose-dependent inhibition of the blastogenic response. Effective inhibition (greater than 50%) of LNC responses to PHA and LPS occurred with concentrations of Fn that ranged from 10-50 micrograms/culture. The proliferative response to Con A was less affected by the presence of Fn: 50% inhibition was observed only with the highest concentration of Fn studied. Fn at low concentrations was more effective than Fn-depleted plasma in inhibiting lymphocyte responses to PHA. Optimal expression of the regulatory activity of Fn occurs during and following the peak proliferative period for both PHA and LPS responses. In order to evoke maximum inhibition it is necessary for Fn to be present within 12 hours following stimulation of LNC with mitogen. Inhibition does not appear to be the result of Fn-mitogen complexes which reduce the amount of mitogen available for stimulation, since increasing concentrations of either PHA or LPS did not significantly reduce the inhibitory effect. Furthermore, inhibition was not influenced by the concentration of fetal calf serum present in the culture medium. Thus, Fn may function as an important nonspecific immunoregulatory factor at inflammatory sites and in areas of tissue repair.
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PMID:Modulation of rat lymphocyte transformation by plasma fibronectin. 665 42

Unstimulated endothelial cell (EC) cultures express low levels of intercellular adhesion molecule-1 (ICAM-1) and their expression can be enhanced by inflammatory cytokines such as tumor necrosis factor alpha (TNF). Three monoclonal antibodies (MoAbs) highly reactive with TNF-stimulated human ECs were established and defined to recognize a 95 kDa cell surface protein specifically expressed on cytokine-activated ECs, which was immunochemically identified as ICAM-1. The quantitative immunoassay of soluble and insoluble ICAM-1 could be performed with two different MoAbs. Secretion of fibronectin or the von Willebrand factor, was not significantly enhanced with TNF stimulation. Cellular expression of ICAM-1 was drastically induced by TNF or interleukin-1 stimulation, and the moderate expression with delayed-action was observed only by lipopolysaccharide stimulation. A maximal amount of soluble ICAM-1 was released from ECs stimulated only by TNF, apparently in a dose dependent manner, but no significant release of ICAM-1 was induced by thrombin interleukin-2, or lipopolysaccharides. Released levels of soluble ICAM-1 from interleukin-1-stimulated ECs were apparently diminished as compared with those from TNF-stimulated cells. These results suggest that release of soluble ICAM-1 from EC surfaces can be most significantly enhanced by TNF-specific signaling, and prospectively, should be a sensitive indicator of intravascular inflammation in acute endothelium injury.
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PMID:Immunoenzymometric analysis for expression and shedding of intercellular adhesion molecule-1 on human endothelial cells stimulated with cytokines or lipopolysaccharide. 753 74

We studied the effects of cytokines such as IL-1 alpha, IL-6 and TNF alpha, and lipopolysaccharide (LPS) on cultured human monocytes. Increased fibronectin (FN) production, as a indicator of the activation of monocytes, was observed with any cytokines or LPS stimulation those were added in the culture medium. These increased FN production by cytokines showed a dose dependent fashion, and 4 hours culture with these cytokines was enough to obtain the amount of FN measured with radioimmunoassay. The combination of sub-optimal dose of cytokines (IL-1 alpha + IL-6, IL-1 alpha, IL-6 + TNF alpha), that could not induce substantial amount of FN with any single cytokine, also could induce FN by cultured monocytes. The specificity of cytokines for the FN production by cultured monocytes was confirmed by the neutralization using monoclonal antibodies specific for each monokines. Northern blot analysis with cDNA specific for FN confirmed the expression of FN mRNA in cultured monocytes stimulated with cytokines or LPS. Cytokine network plays an essential role for immune and inflammatory reaction, and FN has been shown to induce monokines through VLA-5 receptor on cultured monocytes. Our data suggests that monocytes may not always require high concentration of cytokines for the activation of monocytes in vitro, and that the synergistic action of low concentration of cytokines for the activation was enough for the progression of immune or inflammatory reaction.
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PMID:[Cultured human monocytes activated by cytokines or lipopolysaccharide induce fibronectin]. 755 52

Vascular endothelial injury observed in overwhelming sepsis may be caused by neutrophil-derived enzymes. Adherence to the endothelium, a prerequisite for this process, is mediated sequentially by the neutrophil adhesion molecules L-selectin and the beta 2 integrins including CD11b/CD18. The relationship between expression of these molecules, neutrophil adherence, endothelial activation, and consequent endothelial injury was assessed by changes in heparan sulfate and fibronectin matrices. Endothelial prestimulation with lipopolysaccharide caused both an increase in adherence and a generalized reduction in heparan sulfate; disruption of the fibronectin matrix occurred only on the further addition of FMLP. Although maximal disruption of these matrices was associated with elevation of neutrophil CD11b/CD18 and reduction in L-selectin expression, these changes did not determine either the nature or extent of endothelial damage. This model may provide further insights into the interrelationship between neutrophil activation and endothelial damage in gram-negative sepsis.
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PMID:Degradation of glycosaminoglycans and fibronectin on endotoxin-stimulated endothelium by adherent neutrophils: relationship to CD11b/CD18 and L-selectin expression. 768 Jul

Endotoxin (lipopolysaccharide, LPS) is known to induce inflammatory responses, such as monocyte/macrophage adherence, migration, and accumulation. Recruitment and accumulation of macrophages during infection and inflammation are regulated by integrin-mediated cell-extracellular matrix interactions. In the present report, we studied the effects of LPS on the expression of VLA-5 (alpha 5 beta 1), VLA-3 (alpha 3 beta 1), and VLA-2 (alpha 2 beta 1) integrins and fibronectin (FN) by human alveolar macrophages in an attempt to understand the mechanism by which LPS regulates macrophage adhesion to matrix proteins. Bronchoalveolar lavage macrophages were treated with varying concentrations of Escherichia coli LPS for different times and evaluated for expression of the integrins and FN by immunofluorescence, immunoelectron microscopy, autoradiography, and radioimmunoassay. Immunofluorescent and immunoelectron microscopic observations showed that VLA integrins were constitutively expressed on the cell surface and concentrated on the microvilli and pseudopodia of the macrophages. The effects of LPS on expression of the integrins were dose and time related. VLA-5 expression was increased after 30 min of stimulation by LPS, suggesting that LPS may induce rapid secretion of the integrin. However, incubations with LPS longer than 30 min decreased VLA-5 expression in a dose-dependent pattern. LPS also caused dose-related decreases in the expression of VLA-3 and VLA-2 integrins and increases of intracellular FN 24 h after stimulation. The results suggest that a prolonged exposure to LPS may impede VLA integrin-mediated migration and result in local accumulation of macrophages in the lung.
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PMID:Effects of endotoxin on expression of VLA integrins by human bronchoalveolar lavage macrophages. 772 20

Increasing evidence indicates that interaction of cells with fibronectin (Fn) affects many aspects of cellular responses including growth, morphology, differentiation, and activation. However, it is not known whether Fn could activate macrophages for the tumor cell killing. Here we report that Fn provides a signal for murine macrophage activation to tumoricidal activity. Tumoricidal activity was determined by the release of 51Cr from prelabeled P815 mastocytoma target cells. Fn alone had no effect, whereas recombinant interferon-gamma (rIFN-gamma) weakly induced C57BL/6 murine macrophages to kill P815 mastocytoma cells. However, combination of Fn with rIFN-gamma synergized to activate macrophages to lyse tumor cells in a dose dependent manner. Secretion of nitric oxide (NO) correlated with tumor cell killing, and the activated macrophages failed to kill tumor cell targets in the presence of NG-monomethyl-L-arginine (NGMMA), a competitive inhibitor of NO synthase (NOS). Fn, unlike lipopolysaccharide (LPS), alone had no effect on NO synthesis by itself and did not induce bioactive tumor necrosis factor-alpha (TNF-alpha) secretion from murine peritoneal macrophages. The data illustrate the potential for Fn to activate macrophage-mediated antitumor mechanisms in addition to its better characterized role as a cell adhesion molecule.
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PMID:Fibronectin activates murine peritoneal macrophages for tumor cell destruction in the presence of IFN-gamma. 783 12

Nitric oxide (NO) is an important effector molecule of the inflammatory response. It is synthesized by mesangial cells and has been proposed to contribute to glomerular injury in various disease states. We studied whether NO modulates extracellular matrix production in cultured rat mesangial cells. Stimulation of rat mesangial cell NO release with gamma-interferon and lipopolysaccharide resulted in reduced production of collagen (by 35%) fibronectin (by 48%) (P < 0.05). In contrast, laminin synthesis was enhanced two-fold by the same maneuver (P < 0.05). These changes were reversed by the addition of L-NAME, a selective inhibitor of inducible nitric oxide synthase. This is the first demonstration that NO regulates the synthesis of extracellular matrix by mesangial cells. The results indicate that increased renal production of NO in glomerular diseases may attenuate the production and accumulation of matrix proteins and limit the severity of glomerulosclerosis.
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PMID:Nitric oxide modulates the synthesis of extracellular matrix proteins in cultured rat mesangial cells. 785 53

During the course of bovine brucellosis, Brucella abortus adheres to and infects cells of the mononuclear phagocyte system. Potential mechanisms of binding, as measured by numbers of phagocytosed bacteria, were studied in two populations of cattle genetically resistant (R) or susceptible (S) to infection with B. abortus. Live B. abortus gained entry into cultured bovine macrophages without organism-specific opsonization. Bacterial entry into macrophages from R was inhibited by the peptide RGDS, outer membrane-peptidoglycan complex from B. abortus strain RB51, anti-LFA-1 monoclonal antibody, anti-C3 antiserum, fibronectin, purified O-antigen from B. abortus lipopolysaccharide, mannan and heat-aggregated IgG. Bacterial entry into macrophages from S was inhibited by outer membrane-peptidoglycan complex, anti-LFA-1 monoclonal antibody, O-antigen and heat-aggregated IgG. The peptide RGES did not inhibit entry into macrophages from R or S. These data support the existence of organism-related receptors on monocyte-derived macrophages for B. abortus which mediate binding in the absence of serum. Secondly, there are demonstrable differences in mechanisms of binding of B. abortus to cells from cattle genetically resistant or susceptible to infection by this organism. These findings further substantiate the importance of phagocytosis and clearance functions of the mononuclear phagocyte system in resistance to bovine brucellosis. Perpetuation of infection in susceptible cattle may occur by establishing an intracellular reservoir of viable organisms. Further studies are necessary to investigate receptor affinities, and the potential for an alternate receptor for this organism in S cattle.
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PMID:Mechanisms of binding of Brucella abortus to mononuclear phagocytes from cows naturally resistant or susceptible to brucellosis. 794 9


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