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)

Spleen cells of C57B1/6J mice immunized with complete Freund's adjuvant produced macrophage migration inhibitory factor (MIF) when incubated in vitro with tuberculin purified protein derivative (PPD). For optimal MIF production spleen cells were cultured for 48 h in a serum-free medium, at a concentration of 2 x 10(7) cells/ml. MIF was assayed in a xenogenic system, using oil-induced guinea pig peritoneal exudate cells as targets. MIF synthesis could also be induced by pulsing spleen cells for 2 h with concanavalin A, phytohemagglutinin, pokeweed mitogen or lipopolysaccharide, followed by culture in plain medium. No MIF secretion was induced by incubation of spleen cells with anti-theta or rabbit anti-mouse IgG sera. Cells producing MIF in response to PPD were characterized as B cells by virtue of being insensitive to anti-theta serum and complement, by being retained on nylon wool, glass bead and anti-Ig colums and by the presence of Fc receptors. PPD-stimulated T cells did not produce MIF. PPD-induced mouse spleen cell MIF demonstrated a moderate loss of activity by heating at 56 and 80 degrees C and was completely inactivated after digestion with chymotrypsin. By fractionation on Sephadex G-200, migration inhibitory activity was recovered in a molecular range of 100,000-12,400 daltons.
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PMID:Antigen and mitogen induced production of macrophage migration inhibitory factor in the mouse. 37 63

Human T cell hybridomas were constructed by somatic cell fusion in order to dissect molecular heterogeneity of human macrophage activating-factors (MAF). Two stable human hybridoma supernatants contained MAF activity capable of inducing human monocytes tumoricidal without the help of bacterial lipopolysaccharide (LPS). These supernatants in the presence of LPS could also render mouse macrophages tumoricidal. In contrast, recombinant and natural human interferon-gamma (Hu-IFN-gamma) activated human monocytes, but not mouse peritoneal macrophages. The supernatants from the two clones could neither support the growth of human-granulocyte-macrophage colony stimulating factor/human-interleukin-4-dependent (Hu-GM-CSF/Hu-IL-4) cell lines, such as AML 193 and TALL-101, nor stimulate the proliferation of human-interleukin-2-dependent human cell line and lectin-stimulated lymphoblast, which are responsive to human-interleukin-2 and human-interleukin-4. Rabbit or murine antibodies against human-interferon-gamma (Hu-IFN), human-granulocyte-macrophage colony stimulating factor, human interleukin-1 alpha, human-interleukin-1 beta, human-interleukin-6, human-tumour necrosis factor (Hu-TNF), human-lymphotoxin and human-macrophage migration inhibitory factor (Hu-MIF) could not absorb MAF activity. MAF activity in the hybridoma supernatants is associated with the two polypeptides of molecular weights of 70,000-80,000 and 20,000-30,000 daltons, as determined by gel filtration. These results indicate decisively that novel MAF molecule(s) is secreted by human T cell hybridomas.
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PMID:Constitutive production of novel macrophage-activating factor(s) by human T cell hybridomas. 212 37

In vivo exposure of mice to lidocaine (0.25 mg/10 g body weight 4 times a day for 7 days) resulted in impairment of immunocompetent cell function. Spleen lymphocytes removed from animals immediately and 3 days after lidocaine exposure showed changes in their surface charge properties, inhibition of blastogenesis in response to concanavalin A and lipopolysaccharide, and inhibition of antigen-stimulated activation as measured by the mixed lymphocyte reaction. Lymphocytes from animals sensitized to keyhole limpet hemocyanin showed a significantly lower capacity to produce macrophage migration inhibitory factor 8 days after termination of exposure to lidocaine. Animals exposed to the drug were unable to accumulate an adequate number of immunocompetent cells at the site of challenge with a foreign substance (i.e. dextran), and the ability of the animals to destroy tumor cells nonspecifically and specifically was also impaired. The results indicated that chronic exposure to lidocaine resulted in impairment of lymphocyte function, even in the subsequent absence of the drug, and in significant changes in the expression of the immune response.
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PMID:Effect of lidocaine on the function of immunocompetent cells. II. Chronic in vivo exposure and its effects on mouse lymphocyte activation and expression of immunity. 316 Jun 79

Groups of female adult rats were fed either isocaloric protein-free or 18% protein diets for various intervals. Four days before sacrifice, the animals were immunized either with sheep erythrocytes or with a trinitrophenyl-lipopolysaccharide (TNP-LPS) conjugate. Spleen lymphoid cell populations, spleen plaque-forming cells, and serum hemolysins were measured. A persistent diminution, proportional to the duration of protein deprivation, was observed in all parameters studied after immunization with the T-dependent antigen, sheep erythrocytes. The immune dysfunction was more pronounced for hemolysin titers, which became undetectable after 15 days of protein-free diet. The response of the protein-free group to the T-independent antigen (TNP-LPS) after 15 days of diet was only 34% of the control. When a T-cell lymphokine, macrophage migration inhibitory factor, was measured, a normal response was observed in the protein-free group. Feeding a normal diet rapidly restored the spleen plaque-forming cell populations to 60% of normal after 4 days and to 100% after 6 days. Protein starvation influenced the production of antibodies more than it did the number of antibody-forming cells. The nutritional impairment of immunoglobulin synthesis appears to be reversible.
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PMID:T and B lymphocyte function in response to a protein-free diet. 621 14

The mechanism of macrophage activation by Ca2+ ionophore was studied. Peritoneal exudate macrophages from normal guinea pigs exposed continuously to or pulse treated for 1 hr with the ionophore, A23187, were activated, manifesting increased glucose consumption and inhibition of migration. Highly purified macrophages were also activated as effectively as crude macrophage preparations, and the culture supernatant of spleen lymphocytes treated with A23187 lacked a macrophage activating effect, showing that the macrophage activation resulted from the direct effect of A23187 on macrophages, not via lymphokines produced by lymphocytes. The macrophage activation by A23187 was suppressed in the presence of EGTA, but the suppressive effect was overcome by the addition of Ca2+, but not of Mg2+. A dilution experiment with Ca2+ and Mg2+ during the pulse treatment of cells with A23187 revealed that the activating effect of A23187 was more dependent on Ca2+ content than Mg2+. In addition, the Ca2+ antagonist, nicardipine, was found to suppress the activating effect of A23187. The Ca2+ uptake into macrophages was increased by treatment with A23187. These results indicate that Ca2+ influx into cells is primarily important in the macrophage activating effect of A23187. Trifluoperazine (TFP: a specific inhibitor of calmodulin that is an intracellular Ca2+ receptor protein) was found to inhibit the activating effect of A23187. Further, the cyclic nucleotides, dibutyryl-cAMP and -cGMP, did not activate macrophages. Therefore, macrophage activation was presumed not to be directly mediated by cyclic nucleotides. All these findings show that macrophage activation with the ionophore proceeds by the following scheme: Ca2+ influx leads to activation of Ca2+ receptor protein, calmodulin leads to activation of calmodulin-regulated enzymes leads to metabolic changes, activation. TFP was found to suppress the macrophage activation with highly purified guinea pig macrophage activation factor/macrophage migration inhibitory factor (MIF/MAF) or lipopolysaccharide (LPS), suggesting that calmodulin also played an important role in macrophage activation with MIF/MAF or LPS.
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PMID:The mechanism of macrophage activation induced by Ca2+ ionophore. 640 51

Glucocorticoid hormones are important for vital functions and act to modulate inflammatory and immune responses. Yet, in contrast to other hormonal systems, no endogenous mediators have been identified that can directly counter-regulate their potent anti-inflammatory and immunosuppressive properties. Recent investigations of the protein macrophage migration inhibitory factor (MIF), which was discovered originally to be a T-lymphocyte-derived factor, have established it to be a pro-inflammatory pituitary and macrophage cytokine and a critical mediator of septic shock. Here we report the unexpected finding that low concentrations of glucocorticoids induce rather than inhibit MIF production from macrophages. MIF then acts to override glucocorticoid-mediated inhibition of cytokine secretion by lipopolysaccharide (LPS)-stimulated monocytes and to overcome glucocorticoid protection against lethal endotoxaemia. These observations identify a unique counter-regulatory system that functions to control inflammatory and immune responses.
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PMID:MIF as a glucocorticoid-induced modulator of cytokine production. 765 64

For over 25 years, the cytokine known as macrophage migration inhibitory factor (MIF) has been considered to be a product of activated T lymphocytes. We recently identified the murine homolog of human MIF as a protein secreted by the pituitary in response to endotoxin administration. In the course of these studies, we also detected MIF in acute sera obtained from endotoxin-treated, T cell-deficient (nude), and hypophysectomized mice, suggesting that still more cell types produce MIF. Here, we report that cells of the monocyte/macrophage lineage are an important source of MIF in vitro and in vivo. We observed high levels of both preformed MIF protein and MIF mRNA in resting, nonstimulated cells. In the murine macrophage cell line RAW 264.7, MIF secretion was induced by as little as 10 pg/ml of lipopolysaccharide (LPS), peaked at 1 ng/ml, and was undetectable at LPS concentrations > 1 microgram/ml. A similar stimulation profile was observed in LPS-treated peritoneal macrophages; however, higher LPS concentrations were necessary to induce peak MIF production unless cells had been preincubated with interferon gamma (IFN-gamma). In RAW 264.7 macrophages, MIF secretion also was induced by tumor necrosis factor alpha (TNF-alpha) and IFN-gamma, but not by interleukins 1 beta or 6. Of note, MIF-stimulated macrophages were observed to secrete bioactive TNF-alpha. Although previously overlooked, the macrophage is both an important source and an important target of MIF in vivo. The activation of both central (pituitary) and peripheral (macrophage) sources of MIF production by inflammatory stimuli provides further evidence for the critical role of this cytokine in the systemic response to tissue invasion.
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PMID:The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor. 819 15

Cytokines are critical in the often fatal cascade of events that cause septic shock. One regulatory system that is likely to be important in controlling inflammatory responses is the neuroendocrine axis. The pituitary, for example, is ideally situated to integrate central and peripheral stimuli, and initiates the increase in systemic glucocorticoids that accompanies host stress responses. To assess further the contribution of the pituitary to systemic inflammatory processes, we examined the secretory profile of cultured pituitary cells and whole pituitaries in vivo after stimulation with bacterial lipopolysaccharide (LPS). Here we identify macrophage migration inhibitory factor (MIF) as a major secreted protein release by anterior pituitary cells in response to LPS stimulation. Serum analysis of control, hypophysectomized and T-cell-deficient (nude) mice suggests that pituitary-derived MIF contributes to circulating MIF present in the post-acute phase of endotoxaemia. Recombinant murine MIF greatly enhances lethality when co-injected with LPS and anti-MIF antibody confers full protection against lethal endotoxaemia. We conclude that MIF plays a central role in the toxic response to endotoxaemia and possibly septic shock.
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PMID:MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia. 841 54

Cytokines play an important role in inflammation and immunity. In this study, we examined the expression and presence of human macrophage migration inhibitory factor (MIF) in human myelomonocytic leukemia cell line, HL-60 by reverse transcription-polymerase chain reaction (RT-PCR) and immunological methods (Western blot analysis and immunohistochemistry), respectively. The RT-PCR showed that MIF mRNA was constitutively expressed, and the expression was further induced by lipopolysaccharide (LPS) stimulation. The expression was upregulated by LPS at the range of 10 pg/ml to 10 ng/ml; however, it decreased at doses higher than 100 ng/ml. The expression reached the maximum 12 hr after the stimulation, but substantially decreased by 24 hr. Western blot analysis and immunohistochemistry using an anti-human MIF antibody revealed the presence of MIF protein in cytoplasm of the cells. The pathophysiological role of MIF in HL-60 cells has not been fully understood; however, the regulation of MIF mRNA expression by LPS suggests the possibility that the cytokine plays an important role in inflammatory events of leukemia.
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PMID:Identification of macrophage migration inhibitory factor in human leukemia HL-60 cells and its induction by lipopolysaccharide. 895 74

Macrophage migration inhibitory factor (MIF) is an important constituent of the host response to stress and infection and is the first mediator that has been identified to be released from immune cells upon stimulation with glucocorticoids. MIF also has been shown to be secreted from the anterior pituitary gland, monocytes/macrophages, and T cells activated by various proinflammatory stimuli. Once released, MIF acts to counter-regulate the inhibitory effect of glucocorticoids on inflammatory cytokine production. To characterize more precisely the role of MIF in the host response to infection, we undertook a systematic analysis of MIF expression in various organs of the rat after endotoxin (lipopolysaccharide) administration. MIF protein and mRNA were analyzed by immunohistochemistry and in situ hybridization, respectively. MIF was found to be expressed constitutively in organs such as the lung, liver, kidney, spleen, adrenal gland, and skin. Significant quantities of MIF protein were detected preformed in various cell types and appeared to be released as a consequence of endotoxemia. In virtually all tissues examined, the loss of MIF protein 6 hours after lipopolysaccharide administration was accompanied by the induction of MIF mRNA and, at 24 hours, by the restoration of immunoreactive, intracellular MIF. The constitutive production of MIF by several cell and tissue types together with its rapid release from intracellular pools distinguishes MIF from other cytokines or hormonal mediators and significantly expands the physiological role of this unique counter-regulator of glucocorticoid action.
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PMID:Migration inhibitory factor expression in experimentally induced endotoxemia. 900 39


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