UNIPROT:P43026 - FACTA Search

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Query: UNIPROT:P43026 (lipopolysaccharide)
62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Inflammatory disease states predispose to myocardial infarction. Here we have investigated the effects of a systemic inflammatory response syndrome, i.e. lipopolysaccharide (LPS)-induced circulatory shock in rats, on coronary vascular tone. 2. Anaesthetized rats were given LPS (10 mg kg-1, i.v.) and the hearts excised 180 min later for isolated perfusion at constant flow by the Langendorff technique. Once the ex vivo perfusion was started, the perfusion pressure strongly increased in these hearts compared to hearts from control rats (130 +/- 3 vs. 49 +/- 3 mmHg after 10 min). This increase in coronary resistance was not associated with a reduction in endothelial cell function, for the vasodilator responses to bradykinin were unchanged. 3. When hearts were removed 30 min after the injection of LPS, the LPS-induced rise in perfusion pressure was delayed. No changes in perfusion pressure were seen when the hearts were removed 15 min after the injection of LPS. Pre-treatment with cycloheximide or an anti-tumour necrosis factor-alpha (TNF-alpha) antibody or continuous infusion in vivo and in vitro of the endothelin ETA receptor selective antagonist FR 139317, greatly decreased the increase in coronary vascular resistance induced by LPS. 4. These data suggest that TNF-alpha may induce the release of endothelin-1 (ET-1) and that this mediates at least part of the coronary vasoconstriction. This hypothesis is supported by the demonstration that LPS administration increased the circulating levels of both TNF-alpha and ET-1. 5. We conclude, therefore, that in inflammatory disease states, such as LPS-induced septic shock, there is the sequential release of TNF-alpha and endothelin-1 which leads to an increase in coronary vascular tone and so a predisposition to myocardial ischaemia. Inactivation of TNF-alpha by an antibody as well as ETA receptor blockade by a selective antagonist may effectively interfere with this pathway.
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PMID:The contribution of tumour necrosis factor-alpha and endothelin-1 to the increase of coronary resistance in hearts from rats treated with endotoxin. 871 12

Most bacterial and fungal proteases excreted into infected hosts exhibit a wide range of pathogenic potentials ranging from pain, edema or even shock to translocation of bacteria from the site of infection into systemic circulation, thus resulting in septicemia. The basic mechanism or principle common to all these phenomena is explained by kinin generation, either directly from high- and/or low-molecular weight kininogens or indirectly via activation of the bradykinin generating cascade: i.e. Hageman factor-->activated Hageman factor-->prekallikrein-->kallikrein-->high-molecular weight kininogen-->bradykinin. Some bacterial proteases are also involved in activation of other host protease zymogens such as plasminogen, procollagenase (matrix metallo proteases) and proenzymes of the clotting system. Furthermore, most bacterial proteases are not only resistant to plasma protease inhibitors of the hosts, most of which belong to a group of serine protease inhibitors called serpins (serine protease inhibitors), but they also quickly inactivate serpins. Some bacterial proteases may also activate bacterial toxins thus rendering toxigenic pathogenesis. They are also capable of degrading immunoglobulins and components of the complement system and facilitate propagation of micro organisms. All in all, microbial proteases are very critical in enhancing pathogenesis of severe diseases. It is also noteworthy that bacterial cell wall components themselves, i.e. endotoxin (or lipopolysaccharide) of gram negative bacteria and teichoic/lipoteichoic acid of gram positive bacteria, are also able to activate the bradykinin generating cascade-involving activation of Hageman factor as mentioned above.
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PMID:Pathogenic mechanisms induced by microbial proteases in microbial infections. 873 87

Bolus injections of bradykinin (BK, 0.25-1.0 nmol.kg-1 intraarterially (i.a.)) in anesthetized rats produced a dose-dependent hypotensive response, while desArg9-BK (0.25-1.0 nmol.kg-1 i.a.), Lys-desArg9-BK (0.25-1.0 nmol.kg-1 i.a.), and Sar[D-Phe8]desArg9-BK (0.5-1.0 nmol.kg-1 i.a.) were inactive. At 12-24 h after the pretreatment with lipopolysaccharide (10-100 micrograms.kg-1 i.v.), BK produced a greater decrease in blood pressure than in nontreated rats and Sar[D-Phe8]desArg9-BK (0.5-1.0 nmol.kg-1 i.a.) decreased blood pressure by 13.0 +/- 1.0 and 22.2 +/- 2.31 mmHg (1 mmHg = 133.3 Pa), whereas both desArg9-BK and desArg10-kallidin were inactive. The hypotensive effect of BK (0.25-1.0 nmol.kg-1 i.a.) was significantly reduced by HOE-140 (1.0 nmol.kg-1 i.a.) given 5 min before and that of Sar[D-Phe8]desArg9-BK was reduced by [Leu8]desArg9-BK (1.0 nmol.kg-1 i.a.) given 3 min before the agonists. These results indicate that in rats lipopolysaccharide induces B1 receptors in 18 to 24 h. B1 agonists protected from degradation are needed to demonstrate the presence of B1-receptor-mediated hypotension in the rat.
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PMID:Induction of bradykinin B1 hypotensive receptors in rats by lipopolysaccharide. 877 15

The injection of lipopolysaccharide (LPS) from E. Coli into the dorsal skin of rats caused a dose-dependent increase in vascular permeability as measured by the extravasation over a 40-min period of intravenously injected dye. This increase caused by LPS was attenuated by pretreatment with the bradykinin (BK) receptor antagonist HOE140, the selective platelet-activating factor (PAF) antagonist TCV309, and by combined treatment with mepyramine and methysergide. Combined treatment with HOE140 and TCV309 resulted in further suppression than that achieved with a single treatment alone. By the simultaneous pretreatment with all antagonists, the response was almost totally abolished. On the other hand, indomethacin also inhibited the response induced by LPS, but not those induced by BK and PAF itself. A small dose of BK or histamine synergistically potentiated the effect of PAF when simultaneously injected. These results suggest that BK, PAF, histamine/serotonin and prostaglandins are involved in the LPS-induced increase in vascular permeability, where PAF, in addition to its direct action, potentiates the response to BK and histamine, and prostaglandins potentiate the actions of other mediators without its direct action.
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PMID:The mediators involved in endotoxin-induced vascular permeability increase in the rat skin and their interactions. 877 57

To elucidate the mechanism of bacterial exoprotease in promotion of the intravascular dissemination of Pseudomonas aeruginosa, we examined the possible involvement of bradykinin (whose generation is induced by pseudomonal proteases in septic foci) in the invasion by bacteria, and in access of bacterial toxins to systemic blood circulation. P. aeruginosa 621 (PA 621), which produces very little protease, was injected intraperitoneally into mice together with pseudomonal exoproteases (elastase/alkaline protease). Dissemination of bacteria from the peritoneal septic foci to the blood was assessed by counting viable bacteria in the blood and spleen by use of the colony-forming assay. The results showed that pseudomonal proteases markedly enhanced (10- to 100-fold) intravascular dissemination of bacteria in mice. This enhancement was induced not only by pseudomonal proteases but also by bradykinin. More importantly, the increased spread of PA 621 induced by pseudomonal protease and bradykinin was significantly augmented by the addition of kininase inhibitors, indicating the direct involvement of bradykinin in bacterial dissemination. Similarly, bradykinin caused effective dissemination of pseudomonal toxins such as endotoxin (lipopolysaccharide) and exotoxin A when the toxins were injected into the peritoneal cavity with bradykinin. Furthermore, the lethality of the infection with PA 621 was strongly enhanced by pseudomonal proteases given i.p. simultaneously with PA 621. On the basis of these results, it is strongly suggested that pseudomonal proteases as well as bradykinin generated in infectious foci are involved in facilitation of bacterial dissemination in vivo.
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PMID:Bradykinin generation triggered by Pseudomonas proteases facilitates invasion of the systemic circulation by Pseudomonas aeruginosa. 883 27

Bradykinin (BK) and Tyr8-BK induced graded rat paw edema with EC50 values of 1.9 and 1.1 nmol/paw, while des-Arg9-BK (DABK, up to 300 nmol/paw) was marginally effective. Tyr8-BK, but not DABK, also caused a dose-related increase in mouse paw edema, with an EC50 of 1.3 nmol/paw. The response to Tyr8-BK (10 nmol/paw) in rat paw edema was antagonized by B2 receptor antagonists (HOE-140 or NPC 17731, 30 nmol/paw) but not by the B1 antagonist des-Arg9[Leu8]BK (DALBK, 100 nmol/paw). Daily intraplantar injections of Tyr8-BK (10 nmol/paw) for 7 days caused progressive desensitization (D) of edema in sham-operated and adrenalectomized Wistar rats. DABK (100 nmol/paw) caused marked paw edema in D paws from both groups, which was inhibited by DALBK (100 nmol/paw) and by dexamethasone (0.5mg/kg, s.c.). Systemic injection of lipopolysaccharide (10 micrograms/mouse, 24 h prior) potentiated the first and second phases of Formalin-induced pain but had no effect on paw edema. Coinjection of DABK (2-22 nmol/paw) with low doses of Formalin in lipopolysaccharide-treated mice, which had no effect on naive animals, dose dependently potentiated both phases of Formalin-induced pain but did not modify paw edema. These effects were antagonized by DALBK with ID50 values of 21.9 (first phase) and 64.1 (second phase) nmol/paw. Thus, both progressive desensitization of B2 receptors and systemic treatment with lipopolysaccharide induce a glucocorticoid-sensitive upregulation of B1 receptors mediating paw edema in the rat and Formalin-induced nociception in mice. These results suggest that induction of upregulation of B1 receptors may play important roles in controlling inflammatory processes and hyperalgesia.
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PMID:Expression of B1 kinin receptors mediating paw edema and formalin-induced nociception. Modulation by glucocorticoids. 884 14

The purpose of our work was to evaluate the role of bradykinin B2 receptors in the early phase (first 3 h) of bacterial lipopolysaccharide (LPS)-induced shock in anesthetized and mechanically ventilated rabbits and to determine if HOE 140, a specific, potent, and long-acting bradykinin B2-receptor antagonist, could improve survival in two murine models of septic shock. In rabbits, LPS injection induced rapid hypotension associated with metabolic acidosis. Three hours after the injection of LPS, we observed leukopenia, thrombocytopenia, and a moderate increase in arterial blood cyclic GMP. The injection-of HOE 140 [1.7-mumol/kg bolus intravenously (i.v.) 20 min before LPS] inhibited the decrease in blood pressure, but did not influence any of the other parameters studied. Mice were subjected to intraperitoneal (i.p.) injection of LPS, which induced almost 100% mortality in the 4 days after the injection. Pretreatment with HOE 140 (1 mg/kg i.p.) 30 min before the LPS injection and 4, 8, and 24 h afterward the injection did not improve survival at any given time during the 4 days of the study. Cecal ligation and puncture in mice induced a mortality rate > 90% in < or = 10 days. HOE 140 (1 mg/kg i.v.) given 30 min before cecal ligation did not significantly improve the survival rate. In contrast with previous reports, in the present study in a rabbit model of endotoxic shock (early phase) and in two murine models of septic shock, the involvement of bradykinin B2 receptors appeared to be minimal.
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PMID:Bradykinin B2 receptor involvement in rabbit and murine models of septic shock. 884 66

B1 bradykinin receptors were visualized by using the B1 bradykinin receptor agonist [3H]des-Arg10-kallidin in receptor autoradiography experiments. Cryosections were prepared from arterial vessels from a healthy control pig, a pig with pre-existing inflammation and an animal with experimental sepsis induced by an infusion of bacterial lipopolysaccharide (LPS). Only diffusely scattered silver grains with no preference for a distinct tissue structure were detected on emulsion-coated coverslips above the cryosections from the healthy control animal. This indicates that under normal circumstances no or only minute amounts of B1 bradykinin receptors are present in these tissues. In contrast, a 3-fold increase in specific B1 bradykinin receptor binding was observed on both the corresponding preparations of the sick piglet and of that with experimentally induced sepsis. A similar enhancement of specific [3H]des-Arg10-kallidin binding occurred in preparations devoid of endothelium. By comparison with the stained cryosection on the slide the silver grains showed a preferential distribution above smooth muscle cells. Taken together our data are consistent with the hypothesis that B1 bradykinin receptors are induced in the muscle layer of large vessels not only after experimentally-induced sepsis but also in pre-existing inflammatory disease.
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PMID:Autoradiographic visualization of B1 bradykinin receptors in porcine vascular tissues in the presence or absence of inflammation. 885 23

To investigate the influence of inducible nitric oxide synthase on cerebral arteries after subarachnoid haemorrhage (SAH) in vivo, lipopolysaccharide (LPS), a major inducer of inducible nitric oxide synthase, was injected intracisternally into control and SAH model dogs. Intracisternal injection of LPS (0.5 mg) produced a long-lasting, submaximal vasodilation of the basilar artery of control dogs on angiography. This effect became significant at 4 hours after LPS injection and plateaued after 6 hours. This vasodilation was reduced by N(G)-monomethyl-L-arginine. Vasopressin slightly suppressed the vasodilation, while bradykinin increased it. The concentration of L-arginine in CSF decreased after LPS injection, while that of L-citrulline increased. In cytokines, the concentration of tumour necrosis factor-alpha; (TNF-alpha;) in CSF increased transiently at 4 hours after LPS injection, while interleukin-1 beta, interleukin-6, interferon-gamma, did not change. These data suggest that vasodilation by LPS is mainly due to nitric oxide predominantly synthesized by an inducible nitric oxide synthase, proximally induced by TNF-alpha. Our data make it unlikely that SAH itself induces the inducible nitric oxide synthase in vascular tissue, since isolated endothelium-denuded basilar artery from SAH model dogs did not respond to L-arginine. In SAH model dogs, the degree of vasodilation by LPS differed with the severity of vasospasm. Vasodilation was much greater in mild than in severe vasospasm in dogs, and was increased by superoxide dismutase. These findings suggest that the induction of inducible nitric oxide synthase or its activity may be less effective in severe vasospasm.
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PMID:Vasodilation by intrathecal lipopolysaccharide of the cerebral arteries after subarachnoid haemorrhage in dogs. 886 3

The effect of chronic N omega-nitro-L-arginine methyl ester (L-NAME) treatment on the in vivo eosinophil migration induced by bradykinin, platelet-activating factor (PAF), lipopolysaccharide and carrageenin has been investigated in the rat using the pleurisy model. The in vitro (microchemotaxis chamber) eosinophil migration induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP), PAF and zymosan-activated serum was also evaluated in the rat. The eosinophils were obtained from the peritoneal cavity of male Wistar rats and isolated on a discontinuous metrizamide gradient. Chronic inhibition of nitric oxide biosynthesis was achieved by adding L-NAME to the drinking water to give an intake of approximately 75 mumol/rat/day for 4 weeks. Rats treated chronically with L-NAME developed a significant level of hypertension (163 +/- 4.8 mmHg; P < 0.01) compared with animals which received either the same dose of the inactive enantiomer D-NAME (124 +/- 3.2 mmHg) or tap water alone (119 +/- 1.6 mmHg). The intrapleural injection of bradykinin (50 micrograms), PAF (1 microgram), lipopolysaccharide (0.25 microgram) and carrageenin (125 micrograms) into untreated rats in vivo induced a significant level of eosinophil migration by 24 h post-injection. This migration was markedly reduced in L-NAME-treated rats. Eosinophils obtained from untreated rats showed a significant level of migration in vitro in response to fMLP (5 X 10(-8) M), PAF (10(-8) M) and zymosan-activated serum (27 microliters). In contrast, the migration induced by these chemotactic agents was markedly reduced in cells isolated from animals treated chronically with L-NAME. L-Arginine (5.5 mM), but not D-arginine (5.5 mM), restored the ability of eosinophils from L-NAME-treated animals to migrate in response to fMLP. Our results indicate that nitric oxide plays a major role in the in vivo and ex vivo migration of eosinophils.
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PMID:Inhibition of eosinophil chemotaxis by chronic blockade of nitric oxide biosynthesis. 888 18

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