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)

Endothelium and the vascular basement membrane form important barriers between the circulation and extravascular compartment. Cancer cell motility contributes to the passage of metastatic cells across this barrier, an essential step in tumor dissemination. In this study we found that the conditioned media of human endothelial monolayers contained a chemoattractant for neoplastic cells and that the chemoattractant activity was greater in the media of cultures which had been stimulated 4 h previously with 10 micrograms/ml bacterial lipopolysaccharide or the peptide formyl-L-methionyl-L-leucyl-L-phenylalanine at a concentration of 10(-6) M. The generation of this activity correlated with the expression of intracellular mRNA for interleukin 1 (IL-1) and with the presence of IL-1 biological activity in the conditioned media. The chemotactic activity in these media was lost after they had been incubated with anti-IL-1. Finally, recombinant human IL-1 alpha and IL-1 beta stimulated dose-dependent, random, and directed migration of human tumor cell populations in the Boyden chamber assay. Thus, this paper describes a mechanism by which the production of IL-1 by endothelial cells could modulate the behavior of tumor cells within the circulation.
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PMID:Chemotactic activity of endothelial cell-derived interleukin 1 for human tumor cells. 326 92

Mononuclear phagocytes, an integral part of the lymphoreticular infiltrate of human and experimental tumors, might contribute to fibrin deposition within malignant tissues through the production of procoagulant activity (PCA). We have studied the PCA of tumor-associated macrophages (TAM) in 2 poorly immunogenic, metastatic murine sarcomas (mFS6 and MN/MCA1); peritoneal macrophages (PM) from tumor-bearing and control animals were also studied, as reference cell populations. PCA was evaluated by a one-stage clotting assay immediately after isolation (basal PCA) and following in vitro stimulation. Basal PCA was very low (less than 1 U/10(4) macrophages) in all cell preparations. Exposure of PM from both normal and tumor-bearing animals to bacterial endotoxin (lipopolysaccharide, LPS), phorbol myristate acetate (PMA) or the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (FMLP) resulted in 10-, 7- and 3-fold increases in PCA, respectively. In contrast, TAM from mFS6 and MN/MCA1 consistently failed to generate PCA in response to different concentrations of the same stimuli. Treatment of TAM with aspirin did not affect cell unresponsiveness. Fluorescence microscopy showed that almost all PM were stained with fluorescein isothiocyanate (FITC)-LPS, while less than 10% of the TAM were stained. These data, coupled with previous evidence that TAM have a lower number of specific binding sites for phorbol esters than PM, suggest that the defective responsiveness of TAM to endotoxin, PMA and, possibly, FMLP, is due to the lack, or very low expression, of binding sites for these agents on the cell surface. The tumor environment may orient the functional status of in situ macrophages in a direction less favorable to the host.
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PMID:Mouse tumor-associated macrophages do not generate procoagulant activity in response to different stimuli. 327 91

Recombinant human tumour necrosis factor alpha (rHuTNF alpha) was shown to inhibit human neutrophil migration in the presence or absence of a chemotactic gradient generated with the tripeptide, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), at doses of 20-100 U/10(6) cells. In contrast, neither recombinant human interleukin-1 alpha (rHuIL-1 alpha), rHuIL-1 beta, human leucocyte-derived IL-1 alpha (1HuIL-1 alpha) nor 1HuIL-1 beta contained neutrophil migration inhibition properties. However, both the interleukins (1HuIL-1 alpha, 1HuIL-1 beta and rHuIL-1 alpha) and rHuTNF alpha stimulated a neutrophil respiratory burst and significantly elevated the neutrophil respiratory response to fMLP (measured as chemiluminescence and H2O2 production). The stimulatory effects were observed at doses of between 5 and 100 U/5 x 10(5) cells. A characteristic feature of the effects of the cytokines was the range of variation observed in neutrophil responses from different individuals. However, a concentration-related effect was observed with each experiment, delineating suboptimal, optimal and supra-optimal cytokine concentrations. Neutrophils treated with rHuTNF alpha and rHuIL-1 alpha and washed free of exogenous cytokine retained the capacity to show an enhanced response to fMLP. Pretreatment of cells with cytochalasin B enhanced their response to fMLP, and this response was further increased if the cells had also been pretreated with the cytokines. The response to phorbol myristate acetate was also enhanced by rHuTNF alpha and rHuIL-1 alpha. The effects of these cytokines on neutrophils could be abolished by boiling the preparation but not by treating it with polymixin B, suggesting that bacterial lipopolysaccharide was not responsible for the activity of these preparations. The rHuIL-1 alpha increased the release of lysozyme, beta-glucuronidase and myeloperoxidase initiated by cytochalasin B/fMLP, while rHuTNF alpha only increased lysozyme release.
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PMID:Effects of tumour necrosis factor alpha and interleukin-1 alpha and beta on human neutrophil migration, respiratory burst and degranulation. 328 22

The pathogenesis of acute lung injury in humans is obscure, but lipopolysaccharide (LPS), complement activation, and neutrophils have been implicated. We investigated in rabbits the interaction of small amounts of intravascularly administered LPS (100 ng) with neutrophil chemotactic factors, the synthetic chemotactic peptide formyl-norleucyl-leucyl-phenylalanine (FNLP), and the biologically relevant chemotactic fragments of C5 (C5f). These neutrophil stimuli produce neutropenia when injected intravascularly in rabbits, reflecting neutrophil adherence to vascular endothelium. When LPS was injected with FNLP, the duration of neutropenia was enhanced. Studies with radiolabeled neutrophils infused in vivo demonstrated prolonged neutrophil sequestration within the lung in rabbits that were given FNLP plus LPS, an effect that was visible for 4 h after injection. Morphometric analysis of tissue sections 4 h after infusion confirmed the presence of greater numbers of neutrophils in the lungs of animals receiving LPS and FNLP. When a combination of LPS and chemotactic factors was infused at both zero and 6 h, we found a marked enhancement of lung vascular permeability at 24 h (as assessed by radiolabeled albumin accumulation), an effect not seen with either LPS or chemotactic factor alone. Ultrastructural studies revealed neutrophil sequestration and alteration in endothelial cells in the animals that received the combination of LPS and chemotactic factors. Neutrophil depletion with nitrogen mustard completely abolished the increased vascular permeability seen in animals that received LPS and chemotactic factors. This study suggests that small amounts of intravascularly administered LPS enhance the sequestration of neutrophils within the lung and increase lung vascular permeability and endothelial injury caused by neutrophils stimulated by intravascularly administered chemotactic factors. This mechanism may be relevant to the production of acute lung injury in human beings.
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PMID:Neutrophil-mediated pulmonary vascular injury. Synergistic effect of trace amounts of lipopolysaccharide and neutrophil stimuli on vascular permeability and neutrophil sequestration in the lung. 330 Apr 42

The horseshoe crab clotting factor, factor C, present in the hemocytes is a serine-protease zymogen activated with lipopolysaccharide. It is a two-chain glycoprotein (Mr = 123,000) composed of a heavy chain (Mr = 80,000) and a light chain (Mr = 43,000) [T. Nakamura et al. (1986) Eur. J. Biochem. 154, 511-521]. In our continued study of this zymogen, we have now also found a single-chain form of factor C (Mr = 123,000) in the hemocyte lysate. The heavy chain had the NH2-terminal sequence of Ser-Gly-Val-Asp-, consistent with that of the single-chain factor C, indicating that the heavy chain is derived from the NH2-terminal part of the molecule. The light chain had an NH2-terminal sequence of Ser-Ser-Gln-Pro-. Incubation of the two-chain zymogen with lipopolysaccharide resulted in the cleavage of a Phe-Ile bond between residues 72 and 73 of the light chain. Concomitant with this cleavage, the A (72 amino acid residues) and B chains derived from the light chain were formed. The complete amino acid sequence of the A chain was determined by automated Edman degradation. The A chain contained a typical segment which is similar in sequence to a family of repeats in human beta 2-glycoprotein I, complement factors B, protein H, C4b-binding protein, and coagulation factor XIII b subunit. The NH2-terminal sequence of the B chain was Ile-Trp-Asn-Gly-. This chain contained the serine-active site sequence-Asp-Ala-Cys-Ser-Gly-Asp-Ser-Gly-Gly-Pro-. These results indicate that horseshoe crab factor C exists in the hemocytes in a single-chain zymogen form and is converted to an active serine protease by hydrolysis of a specific Phe-Ile peptide bond.
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PMID:Lipopolysaccharide-sensitive serine-protease zymogen (factor C) of horseshoe crab hemocytes. Identification and alignment of proteolytic fragments produced during the activation show that it is a novel type of serine protease. 330 57

Stimulated human monocytes release several proteins thought to play a role in inflammation, including interleukin 1, tumor necrosis factor, and plasminogen activator. We have purified another proinflammatory protein that is chemotactic for human neutrophils from conditioned medium of lipopolysaccharide-stimulated monocytes. After a series of steps that included anion-exchange chromatography, gel filtration, and HPLC on cation-exchange and reverse-phase columns, an apparently pure protein was obtained that migrated as a single 7-kDa band on NaDodSO4/polyacrylamide gels under reducing or nonreducing conditions. The amino acid composition of this monocyte-derived neutrophil chemotactic factor was different from that of interleukin 1 and tumor necrosis factor. N-terminal amino acid sequence of the first 42 residues was determined. This portion of the molecule has up to 56% sequence similarity with several proteins that may be involved in host responses to infection or tissue injury. It is identical to a portion of a sequence deduced from an mRNA induced by staphylococcal enterotoxin treatment of human leukocytes. At the optimal concentration of 10 nM, 50% of neutrophils added to chemotaxis assay wells migrated toward the pure attractant. Potency and efficacy are comparable to that of fMet-Leu-Phe, which is often used as a reference. In contrast to many attractants, the protein was not chemotactic for human monocytes.
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PMID:Purification of a human monocyte-derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokines. 348 May 40

The neutrophil has been implicated as an important mediator of vascular injury, especially after endotoxemia. This study examines neutrophil-mediated injury to human microvascular endothelial cells in vitro. We found that neutrophils stimulated by formyl-methionyl-leucyl-phenylalanine (FMLP), the complement fragment C5a, or lipopolysaccharide (LPS) (1-1,000 ng/ml) alone produced minimal endothelial injury over a 4-h assay. In contrast, neutrophils incubated with endothelial cells in the presence of low concentrations of LPS (1-10 ng/ml) could then be stimulated by FMLP or C5a to produce marked endothelial injury. Injury was maximal at concentrations of 100 ng/ml LPS and 10(-7) M FMLP. Pretreatment of neutrophils with LPS resulted in a similar degree of injury, suggesting that LPS effects were largely on the neutrophil. Endothelial cell injury produced by LPS-exposed, FMLP-stimulated neutrophils had a time course similar to that induced by the addition of purified human neutrophil elastase, and different from that induced by hydrogen peroxide (H2O2). Further, neutrophil-mediated injury was not inhibited by scavengers of a variety of oxygen radical species, and occurred with neutrophils from a patient with chronic granulomatous disease, which produced no H2O2. In contrast, the specific serine elastase inhibitor methoxy-succinyl-alanyl-alanyl-prolyl-valyl-chloromethyl ketone inhibited 63% of the neutrophil-mediated injury and 64% of the neutrophil elastase-induced injury. However, neutrophil-mediated injury was not inhibited significantly by 50% serum, 50% plasma, or purified alpha 1 proteinase inhibitor. These results suggest that, in this system, chemotactic factor-stimulated human neutrophil injury of microvascular endothelial cells is enhanced by small amounts of LPS and may be mediated in large part by the action of neutrophil elastase.
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PMID:Neutrophil-mediated injury to endothelial cells. Enhancement by endotoxin and essential role of neutrophil elastase. 348 59

Glucocorticoids block the localized accumulation of leukocytes as sites of inflammation by preventing their adherence to vascular endothelium. This implies that glucocorticoids are acting either on the leukocytes, endothelium, or cells which produce adherence-promoting factors (such as interleukin 1 (IL-1)). Previous studies have shown that dexamethasone (DEX) treatment of either polymorphonuclear leukocytes (PMN) or human umbilical vein vascular endothelial cells (VEC) or both in vitro does not prevent adherence induced by thrombin or formylmethionyl-leucyl-phenylalanine (f-met peptide). We now show that pretreatment of PMN and/or VEC for 24 hr with 0.1 microM DEX had no effect on adherence of PMN to VEC activated with IL-1 (2 U/ml), lipopolysaccharide (1 microgram/ml), or 12-O-tetradecanoylphorbol-13-acetate (30 ng/ml) suggesting that glucocorticoids may inhibit adherence in vivo by blocking formation of IL-1 and other adherence-inducing stimuli. We have recently established that cultured human lung fragments produce IL-1 in vitro. To investigate whether glucocorticoids could inhibit the production of adherence-inducing factors, we examined the effect of glucocorticoids on IL-1 production from human lung tissue. Treatment of human lung fragments in vitro for 18 hr with glucocorticoids such as DEX and hydrocortisone resulted in dose dependent inhibition of IL-1 production; these and other glucocorticoids, at concentrations ranging between 0.1 and 1 microM, produced greater than 50% inhibition of IL-1 release. Nonglucocorticoid steroids including testosterone and beta-estradiol (1 microM) had no effect. Inhibition of IL-1 production occurred after a lag period 5 of 16 hr, and the relative glucocorticoid potencies agreed with their known anti-inflammatory potencies in vivo (beta-methasone approximately triamcinolone acetonide greater than DEX greater than fludrocortisone greater than prednisolone greater than hydrocortisone). Inhibition of IL-1 production in vivo may, in part, explain the remarkable ability of glucocorticoids to prevent the adherence of leukocytes to endothelium and their accumulation at an inflammatory site.
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PMID:Interleukin 1 production by human lung tissue. II. Inhibition by anti-inflammatory steroids. 349 58

1 The mechanisms by which agents modulate the induction of kinin B1-receptors were investigated by studying the effects of kinins in vitro, by use of the rabbit isolated aorta, and in vivo by measuring the blood pressure of anaesthetized rabbits. 2 The contractile response of the rabbit isolated aorta to kinins increased in a time-dependent manner in vitro. This effect was abolished by continuous exposure to the protein synthesis inhibitor cycloheximide (71 microM). 3 Several substances were found to increase specifically the rate of sensitization to des-Arg9-bradykinin (des-Arg9-Bk), when applied continuously in vitro to tissues isolated from normal animals: bacterial lipopolysaccharide (LPS; 1 micrograms ml-1), muramyl-dipeptide (MDP; 2 micrograms ml-1), phorbol myristate acetate (PMA; 320 nM), epidermal growth factor (EGF; 100 ng ml-1) and endothelial cell growth factor (150 micrograms ml-1). 4 The protease inhibitors phenylmethylsulphonyl fluoride and aprotinin, a non-adjuvant isomer of MDP, rabbit purified leukocyte interferon, fibroblast growth factor and the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) did not have this effect. 5. It has been demonstrated that LPS induces B1-receptors in rabbits enabling des-Arg9-Bk to act as a hypotensive agent. In these experiments neutropenia induced by nitrogen mustard, did not prevent the in vivo effect of LPS. MDP (300 micrograms) and PMA (100 micrograms) were also found to induce a state of responsiveness to des-Arg9-Bk in vivo. FMLP (1 mg i.v.) induced a temporary decrease in blood neutrophil counts but had no effect on the induction of responses to des-Arg9-Bk. 6. The development of responses mediated by the B,-receptor in the two experimental systems seems to be unrelated to the activation of neutrophil leukocytes, but may be related to the activation of tissue macrophages. Approximately 3% of cultured adherent cells derived from rabbit aorta strips following protease digestion were stained for non-specific esterase, supporting such a possibility.
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PMID:Studies on the induction of pharmacological responses to des-Arg9-bradykinin in vitro and in vivo. 367 93

The effect of the migration of bovine blood polymorphonuclear leukocytes (PMNs) in vitro on their phagocytic activity was studied. PMNs were examined before and after migration through various membranes for rosette formation with sensitized sheep erythrocytes to detect Fc receptors (FcRs), phagocytic activity mediated through FcRs with opsonized staphylococci (Smith strain), and phagocytic activity mediated through nonimmunological receptors with unopsonized staphylococci (strain 305). Migration of PMNs was observed from the upper to the lower compartment of the blind well chamber through Millipore and Nuclepore membranes; through Millipore, Nuclepore, and nylon membranes coated with collagen; and through collagen-coated Millipore, Nuclepore, and nylon membranes overlaid with MA-104, BHK-21, MDBK-99, TB, or FBHE cells. Random migration of PMNs toward the plain medium (the same medium in the upper and lower compartments) through the membranes with and without a monolayer of cells increased the percentage of PMNs forming rosettes. In contrast, migration toward the medium containing lipopolysaccharide (LPS), formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP), or zymosan-activated serum (Act. serum) did not change the percentage of PMNs forming rosettes. The increased percentage of PMNs forming rosettes was associated with the enhanced phagocytosis of opsonized staphylococci (mediated by FcRs). In contrast, migration of PMNs toward LPS, FMLP, or Act. serum did not enhance phagocytosis mediated through FcRs. However, PMNs after migration toward LPS, FMLP, Act. serum, and plain medium enhanced phagocytosis of unopsonized staphylococci (mediated through the nonimmunological receptors).
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PMID:Appearance of Fc receptors on polymorphonuclear leukocytes after migration and their role in phagocytosis. 371 May 88


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