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)

The motility of circulating neutrophils from seven patients affected by intermediate and high-grade non-Hodgkin's lymphoma was investigated before and after rhG-CSF administration (5 micrograms/kg/d for 5 d subcutaneously) in the course of chemotherapy. Random motility and bacterial lipopolysaccharide-induced chemotaxis were studied by the micropore filter technique in a Boyden chamber. These functions were evaluated by a very sensitive technique, based on a computer-assisted image processing system, capable of giving several parameters about the kinetics of cell migration. Along with a significant increase in neutrophil number, a significant decrease both in random and stimulated motility was found. The kinetics of cell migration showed that the cells maintained the typical gaussian pattern of random motility. On the contrary, neutrophils were found to have lost the typical stimulated migration peak. These findings are consistent with a rhG-CSF-induced impairment of the directional movement, rather than of the ability of moving at random. These effects were found in patients who, in the same experimental conditions, had displayed an enhanced phagocytosis and phagocytosis-associated chemiluminescence along with an enhanced CD32 expression, not due to an aspecific cell manipulation. Two hypotheses may be taken into account: (i) an increased adhesiveness due to a direct or an indirect activity of the cytokine; (ii) an abnormality in the cytoskeleton maturation and/or rearrangement during the accelerated bone marrow transit of myeloid cells. These findings emphasize that rh-GCSF administration can modulate several functions which play an important role in host defence, and suggest the utility of carrying out further studies to investigate the optimum dosage both to correct neutrophil number and preserve neutrophil functional activities.
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PMID:Motility of rhG-CSF-induced neutrophils in patients undergoing chemotherapy: evidence for inhibition detected by image analysis. 856 91

The rat testis contains a large population of resident macrophages, the physiological roles of which are yet to be established. To investigate the functional capacity of these cells, we have analyzed the secretion of the cytokines interleukin (IL)-1, IL-6, tumor necrosis factor alpha (TNF alpha), and granulocyte macrophage-colony stimulating factor (GM-CSF) by isolated testicular macrophages (TMs) and, for comparison, by isolated rat peritoneal macrophages (PMs). Cells were cultured for 48 h in serum-free medium alone or with lipopolysaccharide (LPS, 10 micrograms/ml) and/or recombinant interferon-gamma (rIFN gamma, 200 U/ml). Specific bioassays were used to measure cytokines in the media collected from cultures. Basal production of IL-1, TNF alpha, and IL-6 by TMs and PMs were similar, but TMs produced 8-fold greater levels of GM-CSF than did PMs. LPS, alone or in combination with IFN gamma, significantly enhanced the secretion of all cytokines by PMs (340-840% increase). LPS alone had little effect on TM secretion except to reduce GM-CSF levels some 4-fold. The addition of LPS and IFN gamma increased IL-1, IL-6, and TNF alpha levels (200-750% increase) and reduced GM-CSF levels to 45% of basal levels. Treatment of cultures with indomethacin to minimize prostaglandin production enhanced the LPS-induced effects in both cell types. Expression of the mRNA for each cytokine in cultures of testicular and peritoneal macrophages, as well as in intact testis, was confirmed by reverse transcription polymerase chain reaction. These studies indicate that macrophages resident within the rat testis have a novel cytokine secretion profile and an altered responsiveness to inflammatory activators compared with macrophages from the peritoneal cavity. This may be important in physiological processes in the testis and may contribute to the dysfunctional afferent immune activity thought to underlie the immunologically privileged status of the testes.
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PMID:Cytokine secretion by macrophages in the rat testis. 856 98

Two carbohydrate-dependent mechanisms exist on alveolar macrophages to clear mannose-containing pathogens: receptor-mediated entry of non-opsonized microorganisms via the mannose receptor and receptor recognition of pathogens opsonized with surfactant-associated protein A (SP-A). A number of studies have demonstrated that mannose receptor expression is tightly linked to the functional state of the macrophage. In the present study, we investigated regulation of binding of SP-A to its receptor on macrophages by the same agents that regulate mannose-receptor expression. Phorbol 12-myristate 13-acetate, lipopolysaccharide (LPS), and interferon-gamma treatment of rat marrow-derived macrophages increased SP-A binding by 163, 296, and 337%, respectively, over untreated controls. Mannose-receptor activity was reduced to 75, 60, and 25% of control levels by these agents. Dexamethasone increased mannose receptor activity to 225%, while decreasing SP-A binding to 44% of controls. Addition of granulocyte macrophage-colony stimulating factor (GM-CSF) to human monocytes on day 0 dramatically increased mannose-receptor activity on day 5 over the non-serum control. SP-A binding was highest to freshly isolated monocytes and decreased to < 10% after differentiation in the presence of GM-CSF. After intraperitoneal injection of dexamethasone, rat alveolar macrophages isolated at 24 h expressed increased mannose-receptor activity and decreased SP-A binding. LPS injection resulted in increased SP-A binding and decreased mannose-receptor activity. In every instance, SP-A binding was inversely regulated with respect to mannose-receptor expression. We therefore speculate that the mannose receptor is a first-line host-defense receptor that is turned off during inflammation. SP-A in the alveolar space can then act as a lung-specific opsonin and mediate clearance of pathogens via the upregulated SP-A receptor.
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PMID:Differential regulation of the mannose and SP-A receptors on macrophages. 857 33

The c-rel protooncogene encodes a subunit of the NF-kappa B-like family of transcription factors. Mice lacking Rel are defective in mitogenic activation of B and T lymphocytes and display impaired humoral immunity. In an attempt to identify changes in gene expression that accompany the T-cell stimulation defects associated with the loss of Rel, we have examined the expression of cell surface activation markers and cytokine production in mitogen-stimulated Rel-/- T cells. The expression of cell surface markers including the interleukin 2 receptor alpha (IL-2R alpha) chain (CD25), CD69 and L-selectin (CD62) is normal in mitogen-activated Rel-/- T cells, but cytokine production is impaired. In Rel-/- splenic T cell cultures stimulated with phorbol 12-myristate 13-acetate and ionomycin, the levels of IL-3, IL-5, granulocyte- macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNF-alpha), and gamma interferon (IFN-gamma) were only 2- to 3-fold lower compared with normal T cells. In contrast, anti-CD3 and anti-CD28 stimulated Rel-/- T cells, which fail to proliferate, make little or no detectable cytokines. Exogenous IL-2, which restitutes the proliferative response of the anti-CD3- and anti-CD28-treated Rel-/- T cells, restores production of IL-5, TNF-alpha, and IFN-gamma, but not IL-3 and GM-CSF expression to approximately normal levels. In contrast to mitogen-activated Rel-/- T cells, lipopolysaccharide-stimulated Rel-/- macrophages produce higher than normal levels of GM-CSF. These findings establish that Rel can function as an activator or repressor of gene expression and is required by T lymphocytes for production of IL-3 and GM-CSF.
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PMID:Rel-deficient T cells exhibit defects in production of interleukin 3 and granulocyte-macrophage colony-stimulating factor. 862 48

Granulocyte-macrophage colony stimulating factor (GM-CSF) is a hematopoietic growth factor with a regulatory effect on the transformation of immature macrophages into multinucleated giant cells (MNGC) that exhibit phenotypic and functional characteristics of osteoclasts (OC). The authors analyzed the bone implant interface membranes harvested from 15 patients with failed total joint replacements for the production and tissue distribution of GM-CSF and interleukin-1 (IL-1). Immunohistology and liquid culture were employed to assess the contribution of these factors in the recruitment of macrophages and the development of bone resorbing MNGC at these sites. This process has been implicated in osteoclastic bone resorption, bone, and bone marrow necrosis adjacent to orthopaedic implants. Histologic assessment of the interface indicated the presence of granuloma and a variable number of MNGC in 11 cases. Four cases showed sites of intramembranous formation of osteoid and mineralized bone that was accompanied by normal bone marrow in two cases. Granulocyte-macrophage colony stimulating factor was expressed by a distinct subset of phagocytic macrophages in the lining layer on the implant side. interleukin-1-positive cells outnumbered those stained for GM-CSF. Stimulation of cultured cells with prosthetic metal particulate material showed marked similarity in the expression of these cytokines to cultures treated with lipopolysaccharide (LPS) or phytohemagglutinin (PHA). The induction of GM-CSF production in the lining layer where small MNGC develop indicates that these cells differentiate locally following the phagocytosis of particulate wear debris. In conclusion, GM-CSF promotes the proliferation and early stages of fusion and development of MNGC responsible for osteolysis at these sites. These results also highlight the capacity of the interface to display both osteogenic and inflammatory characteristics. Collectively, the findings suggest that the local bone marrow could participate in the development of the interface as a source of myeloid cells in addition to the capacity of marrow stroma to generate various osteogenic cells essential for the ingrowth of bone into prosthetic implants.
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PMID:Assessment of the role of GM-CSF in the cellular transformation and the development of erosive lesions around orthopaedic implants. 862 73

NBXFO hybridoma cells produced both the membrane and secreted isoforms of macrophage colony-stimulating factor (M-CSF). Murine bone marrow cells stimulated by the secreted form of M-CSF (sM-CSF) became Mac1+, Mac2+, Mac3+, and F4/80+ macrophages that inhibited the growth of NBXFO cells, but not L1210 or P815 tumor cells. In cytotoxicity studies, M-CSF activated macrophages and freshly isolated macrophages killed NBXFO cells in the presence of polymyxin B, eliminating the possibility that contaminating lipopolysaccharide (LPS) was responsible for the delivery of the cytotoxic signal. Retroviral-mediated transfection of T9 glioma cells with the gene for the membrane isoform of M-CSF (mM-CSF), but not for the secreted isoform of M-CSF, transferred the ability of macrophages to kill these transfected T9 cells in a mM-CSF dose-dependent manner. Macrophage-mediated killing of the mM-CSF transfected clone was blocked by using a 100-fold excess of recombinant M-CSF. Catalase, superoxide dismutase, and the nitric oxide inhibitor, N-omega-nitro-arginine methyl ester (NAME), did not effect macrophage cytotoxicity against the mM-CSF transfectant T9 clones. T9 parental cells when cultured in the presence of an equal number of the mM-CSF transfectant cells were not killed, indicating specific target cell cytotoxicity by the macrophages. Electron microscopy showed that macrophages were capable of phagocytosizing mM-CSF bearing T9 tumor cells and NBXFO hybridoma cells; this suggested a possible mechanism of this cytotoxicity. This study indicates that mM-CSF provides the necessary binding and triggering molecules through which macrophages can initiate direct tumor cell cytotoxicity.
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PMID:Macrophages can recognize and kill tumor cells bearing the membrane isoform of macrophage colony-stimulating factor. 865 38

Adenosine-uridine (AU) instability elements, found in the 3'-untranslated regions of numerous mRNAs, target these mRNAs for rapid degradation. In addition, the degradation rate of some mRNAs that contain AU instability elements can change. This modulation of mRNA stability is an important component in the regulation of expression of many of the cytokines that control the production and function of blood cells. However, it has not been clear whether the stabilities of individual cytokine mRNAs that contain AU instability elements are coordinately regulated or whether different mRNAs can be independently regulated. We have investigated the influence of the cytokine synthesis inhibitory factor interleukin (IL)-10 on the turnover of granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and IL-10 mRNAs in human blood monocytes stimulated with lipopolysaccharide. We find that all three mRNAs are destabilized in response to IL-10 but at different times. The G-CSF and GM-CSF mRNAs respond similarly, being rapidly destabilized, consistent with a direct influence of IL-10 receptor-mediated signals on the stability of these mRNAs. In contrast the IL-10 mRNA became unstable only after several hours of treatment with IL-10, suggesting that the IL-10 mRNA, although it also contains AU instability elements, is not co-regulated with the G-CSF and GM-CSF mRNAs but is regulated by a secondary factor produced in response to IL-10.
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PMID:Differential regulation of the stability of cytokine mRNAs in lipopolysaccharide-activated blood monocytes in response to interleukin-10. 870 32

Astrocytes produce granulocyte/macrophage colony-stimulating factor (GM-CSF) and support the survival and proliferation of microglia. To study the functions of GM-CSF in the central nervous system (CNS), we examined the effects of GM-CSF on cytokine production by glial cells. GM-CSF induced interleukin-6 (IL-6) production by microglia, but not by astrocytes, in a dose-dependent manner as assessed by bioassay and the detection of IL-6 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. GM-CSF did not induce tumor necrosis factor (TNF) alpha or IL-1 in microglia and astrocytes, whereas lipopolysaccharide induced all these cytokines. The induction of IL-6 by GM-CSF in microglia was completely inhibited by antibodies to GM-CSF. Neither IL-3 nor macrophage-CSF (M-CSF) induced IL-6 production in microglia. Given that IL-1 and TNF alpha, monokines derived from microglia, induce IL-6 production in astrocytes, but not in microglia, results indicate that astrocytes and microglia may mutually regulate IL-6 production by different cytokines.
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PMID:Selective induction of interleukin-6 in mouse microglia by granulocyte-macrophage colony-stimulating factor. 872 91

Promyelocytic HL-60 cells differentiated into mature cells when they were cultured in the presence of dimaprit (10(-4) M), a histamine H2 agonist. An injection of Escherichia coli lipopolysaccharide increased the activity of histidine decarboxylase in bone marrow cells in C3H/HeN mice to a much greater extent than in C3H/HeJ mice, which are resistant to various effects of lipopolysaccharide. Histamine production increased concomitantly. In WBB6/F1 (W/W(v)) mice, which are genetically deficient in mast cells, histidine decarboxylase activity increased more than in C3H/HeN mice. Pure (>99% nonspecific esterase, CD14 and Mac-1 positive) macrophage populations were obtained from long-term culture of the bone marrow cells (bone marrow-derived macrophages, BMDM). Culture of the cells in the presence of lipopolysaccharide caused a slight, but dose-dependent increase in histidine decarboxylase-associated histamine synthesis. Granulocyte/macrophage colony-stimulating factor (rmGM-CSF) or interleukin 3 (rmIL-3) potently increased lipopolysaccharide-induced histamine formation.
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PMID:Role of histamine produced by macrophages in mouse bone marrow. 875 Jul 90

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

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