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)

Mononuclear cells derived from chicken peripheral blood or from thioglycollate-induced mouse peritoneal exudates were found to cause calcium release from devitalized homologous bone in vitro. These mononuclear cells with osteolytic activity were adherent to plastic surfaces and were identified as being macrophages by cell surface markers and histochemical staining. Other mononuclear cells such as chicken thymocytes, nonadherent peripheral blood mononuclear cells, and chick embryo fibroblasts did not cause bone dissolution. In parallel with the active solubilization of bone mineral, 14C-label was also released from devitalized calvaria prelabeled with 14C-proline. Macrophages, inactivated by repeated freezing and thawing as well as those cultured in the presence of iodoacetate, did not solubilize bone in vitro. The degree of bone solubilization was directly related to the numbers of macrophages per culture as well as the duration of the culture period. Powdered devitalized homologous bone was used in most experiments, but macrophages were also able to solubilize bone material in vitro from devitalized calvaria and bone slabs. The addition of Escherichia coli lipopolysaccharide to cultures of bone and macrophages significantly increased the levels of calcium released from bone. The addition of parathyroid hormone and calcitonin had no effect on macrophage-mediated bone dissolution. These results suggest that viable macrophages have osteolytic activity and that this activity is modulated by an inflammatory mediator, endotoxin.
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PMID:Bone solubilization by mononuclear cells. 737 9

In the immune system macrophages are the cells responsible for nitric oxide (NO) production. The synthesis of NO by activated macrophages correlates with their cytotoxic effect on neoplastic cells as well as killing of intracellular parasites. In the present paper we test several parameters that may influence (in vitro) NO production by murine peritoneal macrophages previously stimulated in vivo by intraperitoneal injection of thioglycollate. In our system the maximum NO/NO2- release was obtained in the culture containing 10(6) M phi/ml after 24 h incubation. For macrophage activation we used lipopolysaccharide (LPS) and several recombinant cytokines (IFN-gamma, TNF-alpha, IL-2, IL-3, IL-6). We also tested the influence of latex phagocytosis on NO production by simultaneously activated macrophages.
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PMID:An improved experimental model for the study of in vitro release of nitric oxide by murine peritoneal macrophages. 750 53

Bisbenzylisoquinoline (BBI) alkaloids are anti-inflammatory constituents of plants of the families Menispermaceae and Ranunculaceae, which have been used as folk remedies in Japan and China. Five BBI alkaloids (cepharanthine, chondocurine, cycleanine, isotetrandrine and tetrandrine) were tested for suppressive effect on in vitro nitric oxide (NO) production by lipopolysaccharide-stimulated peritoneal macrophages, which were induced with thioglycollate or bacillus Calmette-Guerin in mice. All these BBI alkaloids significantly suppressed NO production at 5 micrograms/mL. Cepharanthine, isotetrandrine and cycleanine were slightly more inhibitory than tetrandrine and chondocurine. The suppression persisted for at least 48 hr. As NO is one of the critical mediators in inflammation, these results may explain some aspects of the anti-inflammatory mechanisms of BBI compounds.
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PMID:Inhibitory effect of bisbenzylisoquinoline alkaloids on nitric oxide production in activated macrophages. 750 81

Bacterial lipopolysaccharide (LPS) has been recognized as one of the most potent activating signals for mouse peritoneal macrophages. In macrophages primed by interferon-gamma (IFN-gamma) or trehalose dimycolate (TDM), LPS induces NO synthase and the events associated with a high nitric oxide output: antitumor and antiparasitic activities. In the present report, it is shown that drugs (calcium ionophores or thapsigargin) which elevate the concentration of cytosolic calcium, [Ca2+]i, induce NO synthase and antitumor activities in primed macrophages, mimicking LPS action. Calcium ionophores and thapsigargin trigger NO synthase activity in macrophages primed in vivo by TDM, in thioglycollate-elicited macrophages primed in vitro by IFN-gamma, and in IFN-gamma-treated EMT6 adenocarcinoma cells. However, activation of TDM-primed macrophages by LPS does not seem to involve calcium fluxes: (i) no change in [Ca2+]i was detectable in TDM-primed macrophages loaded with Fura-2 and exposed to LPS, and (ii) activation of TDM-primed macrophages by LPS can be obtained in the presence of 4 mM EGTA. NO synthase expression is thus controlled in primed macrophages by two different pathways; calcium ionophores can replace LPS but do not act through the same intracellular cascade.
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PMID:Role of calcium in the activation of mouse peritoneal macrophages: induction of NO synthase by calcium ionophores and thapsigargin. 750 25

L-selectin, a cell surface adhesion molecule that is expressed by most leukocytes, mediates leukocyte rolling along vascular endothelium at sites of inflammation. The contribution of L-selectin to leukocyte migration in models of chronic inflammation was assessed by using mice that lack cell surface L-selectin expression. Significant inhibition of neutrophil (56-62%), lymphocyte (70-75%), and monocyte (72-78%) migration into an inflamed peritoneum was observed 24 and 48 h after administration of thioglycollate, an inflammatory stimulus. L-selectin-deficient mice were also significantly impaired in delayed-type hypersensitivity reactions. Footpad swelling in response to sheep red blood cell challenge was reduced 75% in L-selectin-deficient mice compared with wild-type mice. Ear swelling in a model of contact hypersensitivity induced by oxazolone challenge was also reduced by 69% compared to wild-type mice. Consistent with L-selectin-mediating leukocyte migration into diverse vascular beds during inflammation, L-selectin-deficient mice were significantly resistant to death resulting from lipopolysaccharide (LPS)-induced toxic shock. LPS administration resulted in a 90% mortality rate in control mice after 24 h, while there was a 90% survival rate in L-selectin-deficient mice. These results demonstrate that L-selectin plays a prominent role in leukocyte homing to nonlymphoid tissues during inflammation and that blocking this process can be beneficial during pathological inflammatory responses.
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PMID:L-selectin-deficient mice have impaired leukocyte recruitment into inflammatory sites. 753 45

In previous studies, neutrophil-ingesting macrophages were clearly and easily observed in the peritoneal cavity of guinea pigs after intraperitoneal injection of thioglycolate medium, and phagocytosis of neutrophils by macrophages could be detected in in vitro cultures of peritoneal exudate cells. Using an in vitro system, we examined the effect of bacterial lipopolysaccharide and recombinant human granulocyte colony-stimulating factor on the apoptosis (programmed cell death) of neutrophils and their subsequent ingestion by macrophages. Lipopolysaccharide delayed karyopyknosis and apoptosis of neutrophils, as shown by endogenous endonuclease activity and a high proportion of trypan blue-excluding cells, and subsequent ingestion by autologous macrophages. Granulocyte colony-stimulating factor also delayed neutrophil karyopyknosis and ingestion by macrophages. When a thioglycolate medium was coinjected intraperitoneally with lipopolysaccharide into guinea pigs in the in vivo system, delays in neutrophil disappearance and ingestion by macrophages in the peritoneal cavity were also observed. We suggest that bacterial products and cytokines regulate neutrophil apoptosis and subsequent ingestion by macrophages at inflamed sites.
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PMID:Lipopolysaccharide and granulocyte colony-stimulating factor delay neutrophil apoptosis and ingestion by guinea pig macrophages. 768 99

Although several murine macrophage (m phi) cell lines from different sites have previously been obtained by in vitro infection with the J2 murine retrovirus, which carries the v-raf and v-myc oncogenes, it was not possible to immortalize thioglycolate-elicited peritoneal macrophages (Pm phi s) by this in vitro procedure. A technique utilizing in vivo injection of the J2 virus has been developed to overcome this problem. The J2 virus immortalized Pm phi s in a very efficient manner in vivo because no exogenous growth factors were required for the in vitro proliferation of these cells and numerous continuous cloned cell lines were readily established. In contrast, Pm phi s obtained from uninfected mice or Pm phi s infected in vitro with the J2 virus did not proliferate. The in vivo immortalized cells had many of the morphological and functional characteristics of m phi s. Analysis of two of the clones, PMJ2-PC and PMJ2-R, demonstrated intracellular expression of the product of the v-raf gene, presence of m phi-associated cell surface antigens, interleukin-6 secretion induced by lipopolysaccharide, and biological response modifier-induced cytotoxic activity against tumor cells. In addition, one of the clones, PMJ2-PC, constitutively expressed major histocompatibility complex (MHC) class II antigens, and in the other clone, PMJ2-R, MHC class II antigens expression was induced by recombinant murine interferon-gamma. This method of utilizing the J2 virus in vivo represents a novel technique for obtaining hematopoietic cell lines from cells that are difficult to immortalize in vitro.
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PMID:In vivo immortalization of murine peritoneal macrophages: a new rapid and efficient method for obtaining macrophage cell lines. 768 28

Strong evidence supports the concept that lipid A is the main biologically active region of endotoxins and is recognized by specific binding sites of different cell types. However, receptors for carbohydrates are also present on mononuclear phagocytes, and it has been suggested that one of these lectin-like proteins may be specific for the 3-deoxy-D-manno-2-octolosonic acid (Kdo) residues of endotoxins. To reexamine this hypothesis, we prepared a 125I-labeled conjugate consisting of a synthetic Kdo-2,4-Kdo disaccharide covalently linked to bovine serum albumin (125I-Kdo2-BSA). The Kdo disaccharide residues of this radiolabeled conjugate were fully accessible to a monoclonal antibody which reacts specifically with this epitope. However, 125I-Kdo2-BSA did not exhibit any detectable specific binding on thioglycolate-elicited mouse peritoneal macrophages or on human monocytes. Furthermore, the specific binding of biotin-labeled lipopolysaccharide derivatives to mouse macrophages and human monocytes was not inhibited by a soluble synthetic Kdo-2,4-Kdo-polyacrylamide copolymer or by a synthetic glycolipid consisting of an alpha-Kdo residue glycosidically linked to O-6 of allyl-4-O-phosphoryl-N-3-hydroxytetradecanoyl-beta-D-glucosaminide. These results indicate that binding sites specific for Kdo are not present (or not accessible) on the surface of mouse macrophages and human monocytes.
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PMID:A synthetic analog of the 3-deoxy-D-manno-2-octulosonic acid disaccharide moiety of rough-type endotoxins does not bind to mouse peritoneal macrophages and human monocytes. 768 37

We studied the effects of microbial products on glucose consumption and morphology of macrophages which were elicited with thioglycollate medium. Macromolecules such as lipopolysaccharide (LPS), tumor promoters, and respiratory inhibitors increased macrophage glucose consumption without inducing evident morphological changes. The assay system was used to screen for active substances in culture broth extracts from actinomycetes. Among them, aureothin increased glucose consumption of macrophages and inhibited respiration of a rat mitochondrial fraction. Concanamycin A induced morphological changes of macrophages into needle-like shapes but not of cloned cells including the macrophage-like cells J774.1. This compound changed fibrosarcoma L929 cells into round shapes without affecting the shape of a nontransformed fibroblast, BALB/3T3 cells. Antimycin and concanamycin A increased tumor-killing activity of macrophages when added during the effector phase. These results suggest that this assay system is simple and sufficiently reproducible and thus usable for screening for modulators of macrophage function among natural products.
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PMID:Effects of microbial products on glucose consumption and morphology of macrophages. 776 60

This study investigated the role of activated macrophages (M phi) in nitric oxide (NO) production and the tumoricidal effect of NO on glioma cells. Induced peritoneal M phi were prepared 6 days following the injection of thioglycollate broth into C3H/He N (H-2 kappa) mice. M phi were activated in vitro recombinant human interferon-gamma (IFN gamma) and lipopolysaccharide (LPS) into the culture medium of the elicited M phi. Two kinds of murine malignant glioma cell lines, RSV-M glioma (H-2 kappa) and VM-glioma (H-2b) were used as targets. P815 mastocytoma cells (H-2d) were used as a control target, since they are insensitive to tumor necrosis factor-alpha, but susceptible to NO derived from M phi. L-arginine-depleted medium was used to inhibit NO-mediated cytocidal activity against tumor cells. Cytotoxicity was assayed at various effector-to-target ratios using an admixture of M phi and 1.5 x 10(4) 125I-labeled target cells 48 hours following co-culture. NO was measured in culture medium using Griess reagent, and the concentration of NO was expressed as mu mol/ml NaNO2. Peritoneal M phi induced only 10% and 15% lysis of RSV-M glioma and VM glioma cells, respective, and LPS augmented this killing activity of M phi to a maximum of 1.2 to 1.4 fold in a dose-dependent manner with dosages from 1 to 50 ng/ml. LPS demonstrated a synergistic action on M phi-mediated cytotoxicity 4 hours following pretreatment with IFN gamma. Alternatively, low doses of IFN gamma alone had no enhancing effect on M phi tumoricidal activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Role of nitric oxide produced by activated macrophages in their cytocidal activity against glial tumor cells]. 777 2


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