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)

Four basic neutrophil chemotactic factors (chemokines) have been purified from conditioned medium of granulation tissue obtained from carrageenin-induced inflammation in the rat. On the basis of their N-terminal amino acid sequences, one of the chemokines was identical with rat GRO/cytokine-induced neutrophil chemoattractant (CINC) which we reported previously, and another was identical with rat macrophage inflammatory protein-2 (MIP-2). Two other chemokines were novel chemoattractants related to MIP-2. The novel chemokines are referred to as rat GRO/CINC-2 alpha and CINC-2 beta, and consequently CINC and rat MIP-2 are renamed rat GRO/CINC-1 and CINC-3 respectively. The complete amino acid sequences of purified CINC-2 alpha and CINC-3 were determined by analysis of the fragments isolated from proteinase V8-treated CINCs. The cDNA for CINC-2 beta was cloned by reverse transcription/PCR amplification using specific primers starting with total RNA extracted from lipopolysaccharide-stimulated rat macrophages. A comparison of the amino acid sequence encoded by the cDNA with the N-terminal amino acid sequence of purified CINC-2 beta revealed that mature CINC-2 beta is a 68-residue chemoattractant produced by cleavage of a 32-residue signal peptide. The difference in amino acid sequences between CINC-2 alpha and CINC-2 beta consisted of only three C-terminal residues. Rat GRO/CINC-2 alpha is a major chemokine, and the four purified chemokines have similar chemotactic activity, suggesting that they contribute to neutrophil infiltration into inflammatory sites in rats.
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PMID:Identification of cytokine-induced neutrophil chemoattractants (CINC), rat GRO/CINC-2 alpha and CINC-2 beta, produced by granulation tissue in culture: purification, complete amino acid sequences and characterization. 804 1

Using a rat model of acute lung inflammation induced by intratracheal instillation of lipopolysaccharide (LPS), we investigated the kinetics of mRNA expression and the potential cellular sources of tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2), interleukin (IL)-1 beta, IL-6, RANTES, and transforming growth factor-beta 1 (TGF-beta 1). By Northern blot analysis, TNF-alpha and MIP-2 mRNAs in total lung tissue increased markedly by 30 min and peaked by 1 h after LPS exposure, whereas expression of IL-1 beta and IL-6 was not detected until 1 h and peaked within 6 h. In contrast, neither RANTES nor TGF-beta 1 mRNA was induced by LPS throughout 72 h, although a basal expression was detected in both saline- and LPS-treated lung tissues. At 1 h after LPS, the bronchoalveolar lavage (BAL) fluid contained about 98% alveolar macrophages (AM), whereas by 6 or 12 h, 88% of BAL cells were polymorphonuclear neutrophils (PMN). Upon extraction of total RNA after separation of AM from PMN in BAL, Northern analysis showed that at 1 h, AM expressed pronounced signals for TNF-alpha, MIP-2, IL-1 beta, and IL-6. At 6 and 12 h, however, while cytokine transcripts decreased in AM, PMN exhibited strong signals for these cytokines. A low basal noninducible signal for TGF-beta 1 but not RANTES was detected in both AM and PMN. Finally, by in situ hybridization techniques, PMN in the lung tissue, particularly those located in the vicinity of the bronchiole and vasculature, were demonstrated to localize MIP-2 mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokine expression by neutrophils and macrophages in vivo: endotoxin induces tumor necrosis factor-alpha, macrophage inflammatory protein-2, interleukin-1 beta, and interleukin-6 but not RANTES or transforming growth factor-beta 1 mRNA expression in acute lung inflammation. 811 Apr 70

We examined the synthesis and release of MIP-1 alpha in alveolar macrophages obtained from normal subjects or subjects infected with HIV-1, at different stages of the disease. HIV-1-infected subjects in groups II, III and IV all had significant interstitial pneumonitis, featuring a significant infiltration of CD8+ lymphocytes in the bronchoalveolar lavage. Alveolar macrophages from HIV-1-infected subjects were shown to express significant levels of MIP-1 alpha via immunohistochemistry, both spontaneously and in response to lipopolysaccharide (LPS), whereas cells from normal subjects expressed very low levels of the cytokine. Supernatants of alveolar macrophages from HIV-1-infected subjects exerted strong chemotactic activity for purified activated blood CD8+ T lymphocytes, which was strongly inhibited by neutralizing MIP-1 alpha. Studies of patients with HIV-1 infection at different stages of the disease showed that MIP-1 alpha secretion increased as viral infection developed. There was a significant positive correlation between MIP-1 alpha secretion and the CD8+ alveolitis in HIV-1-infected subjects. Infection of alveolar macrophages in vitro with three distinct strains of HIV-1 which replicated profusely in macrophages did not induce the expression of MIP-1 alpha. Collectively, these data suggest that HIV-1 infection in vivo induces MIP-1 alpha expression and release in alveolar macrophages, and this appears to contribute significantly to the alveolar lymphocytosis seen in HIV-1-infected subjects.
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PMID:Alveolar macrophages from subjects infected with HIV-1 express macrophage inflammatory protein-1 alpha (MIP-1 alpha): contribution to the CD8+ alveolitis. 818 26

A number of disease states are characterized by the accumulation of inflammatory cells at the site of tissue injury. Mononuclear phagocytes (M phi) represent key cellular mediators of inflammation via the production of regulatory and chemokinetic cytokines. One such cytokine, macrophage inflammatory protein-1 alpha (MIP-1 alpha), has been shown to be one of the major inducible chemotaxins expressed from murine macrophage cell lines (RAW 264.7). We postulated that MIP-1 alpha is a major monocyte chemoattractant produced by resident M phi, and the magnitude of production of this chemotaxin may depend upon the specific population of M phi studied. To test this hypothesis, we isolated alveolar macrophages (AM phi) and peritoneal macrophages (PM phi) from CD-1 mice by bronchoalveolar and peritoneal lavage, respectively. Recombinant murine MIP-1 alpha accounted for significant neutrophil chemokinetic rather than chemotactic activity, as assessed by checkerboard analysis. LPS-stimulated AM phi-derived monocyte chemotactic activity (MCA) was significantly neutralized by specific rabbit anti-murine MIP-1 alpha serum. In contrast, PM phi-derived conditioned media failed to produce MCA attributable to MIP-1 alpha. The production of MIP-1 alpha was then characterized from both AM phi and PM phi. While unstimulated AM phi and PM phi failed to express MIP-1 alpha mRNA, both AM phi and PM phi challenged with lipopolysaccharide (LPS) expressed MIP-1 alpha mRNA in a time-dependent fashion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression and regulation of macrophage inflammatory protein-1 alpha by murine alveolar and peritoneal macrophages. 829 85

Neutrophil (polymorphonuclear leukocyte [PMN]) sequestration is one of the histologic hallmarks of an acute inflammatory response. During the natural evolution of an inflammatory response, PMNs are often replaced by mononuclear cells. This shift in the elicitation of specific leukocyte populations usually occurs as the inflammatory lesion enters either the repair/resolution stage or progresses to a chronic inflammation. To elucidate a potential mechanism for the temporal change from predominantly PMN recruitment to the presence of monocytes, we postulated that PMNs could be a rich source of monocyte chemotactic factors. In our studies, we have identified a dose-dependent induction of monocyte chemotactic activity by PMNs treated with lipopolysaccharide (LPS; 1-100 ng/ml). Interestingly, this monocyte chemotactic activity was significantly attenuated in the presence of neutralizing anti-human macrophage inflammatory protein 1 alpha (MIP-1 alpha) antibodies. Moreover, immunolocalization studies demonstrated the expression of MIP-1 alpha by stimulated PMNs. These findings showed that a significant amount of PMN-derived monocyte chemotactic activity was attributable to MIP-1 alpha. Subsequent characterization of MIP-1 alpha steady-state mRNA and antigen expression demonstrated both a dose- and time-dependent production by LPS-treated PMNs. Granulocyte/macrophage colony-stimulating factor (GM-CSF), a potent PMN activator, failed to induce the expression of MIP-1 alpha over a wide range of concentrations. However, PMNs stimulated in the presence of both LPS and GM-CSF resulted in a synergistic expression pattern for MIP-1 alpha. PMNs stimulated in the presence of both GM-CSF and LPS demonstrated an enhanced and prolonged expression for both MIP-1 alpha mRNA and antigen, as compared with LPS alone. Messenger RNA stabilization analyses demonstrated that MIP-1 alpha mRNA isolated from PMNs stimulated in the presence of GM-CSF and LPS had a prolonged mRNA t1/2, as compared with LPS alone. These findings support the notion that PMNs are capable of producing MIP-1 alpha in the presence of LPS, and that GM-CSF can influence this production through prolongation of MIP-1 alpha mRNA t1/2. The production of PMN-derived MIP-1 alpha, in association with the expression of appropriate adhesion molecules at a site of inflammation, may be one of the central events that contributes to the temporal shift from predominantly PMNs to monocytes during the evolution of inflammation.
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PMID:Expression and regulation of human neutrophil-derived macrophage inflammatory protein 1 alpha. 831 95

Mononuclear phagocytes are essential cellular mediators of both acute and chronic inflammatory responses. In addition to producing substances that mediate tissue injury directly, such as proteolytic enzymes and oxygen radical species, mononuclear phagocytes can secrete proteins involved in the activation and recruitment of inflammatory cells. One of the major inducible polypeptides secreted by mononuclear phagocytes is macrophage inflammatory protein 1 (MIP-1). Native MIP-1 is a protein with leukocyte chemotactic and stimulatory activity. MIP-1 consists of two highly homologous peptides, MIP-1 alpha and MIP-1 beta. We now characterize the expression of MIP-1 alpha from human peripheral blood monocytes (PBM) and identify the T-lymphocyte product interleukin-4 (IL-4) as an important regulator of MIP-1 alpha expression from PBM. In initial experiments, we demonstrated the production of MIP-1 alpha from lipopolysaccharide (LPS)-, interleukin-1 (IL-1)-, and phytohemagglutinin (PHA)-stimulated PBM. IL-4 inhibited the production of MIP-1 alpha from LPS-, IL-1-, and PHA-challenged PBM by 63, 81, and 88%, respectively. The suppressive effects of IL-4 were operative at the level of MIP-1 alpha mRNA, which was reduced in a dose-dependent fashion by IL-4. The suppression of MIP-1 alpha mRNA by IL-4 was observed within a narrow temporal window and was dependent upon the de novo synthesis of a protein intermediate. As determined by mRNA stability studies, IL-4 decreased steady-state levels of MIP-1 alpha mRNA, in part, by accelerating MIP-1 alpha mRNA decay.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gene expression of macrophage inflammatory protein-1 alpha from human blood monocytes and alveolar macrophages is inhibited by interleukin-4. 833 86

Macrophage inflammatory proteins 1 alpha and 2 (MIP-1 alpha, MIP-2) are members of a growing family of cytokines thought to play a role in host defense. MIP-1 alpha and MIP-2 were previously identified in the mouse and shown to stimulate inflammatory cell recruitment. To better understand the potential role of MIP-1 alpha and MIP-2 in lung defense, we investigated the ability of rat lung cells to express mRNA for and/or secrete MIP-1 alpha and MIP-2 proteins in vitro and characterized expression of these cytokines in rat lung after in vivo exposure to silica (SiO2) or titanium dioxide (TiO2). In response to lipopolysaccharide, rat alveolar macrophages expressed increased levels of MIP-1 alpha and MIP-2 mRNA and secreted proteins (identified by N-terminal sequencing) homologous to mouse MIP-1 alpha and MIP-2. Rat alveolar macrophage MIP-1 alpha and MIP-2 mRNA expression was also increased by tumor necrosis factor-alpha (TNF) and adherence to plastic. Studies with a rat fibroblast and epithelial cell line demonstrated that MIP-2, but not MIP-1 alpha, expression can be detected in these cells after stimulation with TNF. Intratracheal instillation studies with SiO2 and TiO2 showed that inflammatory doses of these dusts increase MIP-1 alpha and MIP-2 mRNA expression in whole lung and that increased gene expression preceded the accumulation of inflammatory cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Macrophage inflammatory proteins 1 and 2: expression by rat alveolar macrophages, fibroblasts, and epithelial cells and in rat lung after mineral dust exposure. 838 10

Macrophage inflammatory protein 1 alpha (MIP-1 alpha) is a 6-8-kD, lipopolysaccharide-inducible monocyte and neutrophil chemotactic protein that may be important in acute and chronic inflammation. The present study determined the sequential production, source, and in vivo contribution of murine MIP-1 alpha in synchronized Schistosoma mansoni egg pulmonary granuloma formation. Granulomas were examined under conditions of primary, secondary vigorous, and secondary immunomodulated immunity. Secreted MIP-1 alpha was measured in 24-h supernatants from intact granulomas (700/ml) cultured with or without soluble egg antigen (SEA). Primary granulomas isolated from naive mice over a 16-d period showed low spontaneous MIP-1 alpha production (< 1 ng/ml). However, when primary granulomas were challenged with SEA, significant MIP-1 alpha production was observed beginning at day 4 and peaking at day 16. Intact vigorous (isolated from 8-wk-infected mice) and modulated (isolated from 20-wk-infected mice) secondary pulmonary granulomas demonstrated comparable spontaneous MIP-1 alpha production. Addition of SEA to vigorous stage granulomas augmented expression of MIP-1 alpha at all time points, whereas stimulated modulated stage granulomas did not increase production. The latter observation is likely related to endogenous immunoregulatory mechanisms reported for modulated stage animals. Immunohistochemical localization of MIP-1 alpha in granuloma sections and cytocentrifuge preparations from vigorous lesions localized MIP-1 alpha production to macrophages within granulomas. Treatment of mice with rabbit anti-mouse MIP-1 alpha antibodies significantly decreased 8-d primary granuloma formation (> 40%) when compared with control mice. Anti-MIP-1 alpha sera also decreased vigorous (> 20%), but not modulated granuloma formation. These findings demonstrate that MIP-1 alpha contributes to cellular recruitment during schistosome egg granuloma formation.
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PMID:The role of macrophage inflammatory protein 1 alpha in Schistosoma mansoni egg-induced granulomatous inflammation. 849 76

Potent chemotactic activity for neutrophils was detected in rat inflammatory exudate induced by a subcutaneous injection of lipopolysaccharide in a carboxymethyl-cellulose suspension. We purified and characterized chemoattractants from the exudate by the following procedures: carboxymethyl-Sephadex C-25 ion-exchange chromatography; G3000SW gel-filtration chromatography; preparative reverse-phase high-pressure liquid chromatography; rechromatography on reverse-phase HPLC. Two chemotactic factors were purified and their N-terminal amino acid sequences were determined. One factor was a protein in which the first 20 N-terminal amino acids were identical to those of rat cytokine-induced neutrophil chemoattractant (CINC), a counterpart of human gro/melanoma growth-stimulating activity (MGSA). The other factor was highly similar to mouse macrophage inflammatory protein 2 (MIP-2). Mouse MIP-2, a chemotactic factor for neutrophils, is a member of the interleukin-8 family; however the protein we purified had higher similarity to human gro/MGSA than to human interleukin-8. These results indicate that, in rats, chemotactic factors for neutrophils induced by lipopolysaccharide stimulation are not counterparts of interleukin-8, but are gro/CINC-related peptides.
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PMID:Chemoattractants for neutrophils in lipopolysaccharide-induced inflammatory exudate from rats are not interleukin-8 counterparts but gro-gene-product/melanoma-growth-stimulating-activity-related factors. 850 97

The aim of this study was to measure the level of cytokines produced by peripheral blood mononuclear cells (PBMNC) in patients with aplastic anemia (AA) and to determine their effect on the clonal growth of normal bone marrow (BM) cells. Twenty-one patients with AA and 11 normal controls were enrolled in this study. Medium conditioned by PBMNC of AA patients in the presence of lipopolysaccharide (LPS) was found to be suppressive to the colony growth of normal BM cells. Thus, we further determined the presence in the PBMNC-conditioned medium (CM) of both inhibitory cytokines: macrophage inflammatory protein-1 alpha (MIP-1 alpha), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta 2 (TGF-beta 2), and interferon-gamma (IFN-gamma), and stimulatory cytokines: interleukin-3 (IL-3) and stem cell factor (SCF). Spontaneous production of MIP-1 alpha was higher in the AA patients than the normal controls (1887 +/- 174 pg/ml vs 1643 +/- 93 pg/ml), but the difference was not significant. After LPS stimulation, the production of MIP-1 alpha was markedly increased in the AA patients, and its level was significantly higher than that of the normal controls (2360 +/- 149 pg/ml vs 1517 +/- 92 pg/ml, p = 0.0022). The level of TNF alpha was also higher in the AA patients. However, IFN-gamma, TGF-beta 2, SCF, and IL-3 were not detectable in the PBMNC-CM of either AA patients or normals. The myelopoietic suppressing effect of AA-PBMNC-CM from each AA patient was significantly blocked by pretreatment with anti-TNF-alpha, resulting in a colony-forming enhancement of 174% +/- 12%. A similar effect was noted in six of 11 AA patients by pretreatment with anti-MIP-1 alpha. We conclude that TNF alpha and MIP-1 alpha can be overproduced by the PBMNC of some AA patients, which may play a role in the progression of AA.
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PMID:Overproduction of inhibitory hematopoietic cytokines by lipopolysaccharide-activated peripheral blood mononuclear cells in patients with aplastic anemia. 853 59


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