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)

We measured intracytoplasmic free calcium ion concentration ([Ca3+]i) of alveolar macrophages (AMs) in order to elucidate the mechanism(s) of lipopolysaccharide (LPS)-hyperresponsiveness of AMs in patients with sarcoidosis at the second messenger level. Resting [Ca2+]i was higher in patients with sarcoidosis than in normal subjects. [Ca2+]i increase responses were also elevated in patients with sarcoidosis when AMs were stimulated with either anti-CD14 (a LPS/LPS-binding protein complex receptor) antibody, anti-CD64 (Fc gamma receptor I), antibody or platelet activating factor. After incubation with interferon-gamma, resting [Ca2+]i and increase in [Ca2+]i induced by anti-CD14 antibody stimulation were higher in patients with sarcoidosis as compared with values before incubation. Thus, these data suggest that activation of AMs at the second messenger level induced by IFN gamma, at least in part, accounts for LPS-hyperresponsiveness in sarcoidosis.
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PMID:[Alveolar macrophages and granuloma formation]. 128 54

Tumour Necrosis Factor alpha (TNF/Cachectin) is a cytokine produced mainly by macrophages, which has been shown to cause endothelial cell damage, pyrexia and weight loss, clinical features of tuberculosis, but not of sarcoidosis which is in many other respects a similar disease. 1,25 di-hydroxy Vitamin D and gamma interferon, factors which are present in vivo in both tuberculosis and sarcoidosis, enhance the ability of macrophages to release TNF in vitro. We have studied the ability of pulmonary alveolar macrophages (PAM) harvested by broncho-alveolar lavage (BAL) to produce TNF in response to stimulation with E. coli endotoxin lipopolysaccharide (LPS). 25 patients undergoing bronchoscopy and BAL were studied: 9 with sarcoidosis, 7 with tuberculosis (TB) and 9 (non-neoplastic) disease controls. TNF was assayed by Enzyme Linked Immunosorbent Assay (ELISA) in lavage fluid and cell culture supernatants. No TNF was detected in lavage fluid from any of the groups. PAMs from control patients released no detectable TNF spontaneously, but released 59 +/- 31 units after LPS stimulation. Cells from patients with sarcoidosis and tuberculosis released TNF spontaneously in vitro (TB 226 +/- 106 units; Sarcoidosis 293 +/- 176). TNF release by these cells was not increased further by addition of an optimal concentration of LPS. Thus, the pulmonary macrophages of patients with sarcoidosis and tuberculosis released significantly more TNF than those of controls.
Sarcoidosis 1992 Mar
PMID:Tumour necrosis factor production by alveolar macrophages in pulmonary sarcoidosis and tuberculosis. 134 39

Under normal conditions, the release of interleukin 1 (IL-1) and IL-1 inhibitors play a role in tissue homeostasis. We have already reported an increase in IL-1 activity and a decrease in IL-1 inhibitory activity (IHA) in the supernatants of alveolar macrophages from healthy long-term smokers as compared with healthy nonsmokers. In this study, we report an alteration in the release of IL-1 and IL-1 IHA from alveolar macrophages in patients with interstitial lung diseases (sarcoidosis and idiopathic pulmonary fibrosis [IPF]). IL-1 activity released from alveolar macrophages stimulated by lipopolysaccharide was increased in patients with active sarcoidosis (mean +/- SD, 2.52 +/- 1.33 U/ml [n = 6] vs 1.38 +/- 0.62 U/ml [n = 15] for healthy non-current smokers [HNS]; p less than 0.05). IL-1 IHA released from alveolar macrophages was significantly different among the groups examined: a decrease of IL-1 IHA occurred in patients with active sarcoidosis (61.4 +/- 19.2 [n = 6] vs 85.9 +/- 13.9 percent:HNS; p less than 0.05) and IPF (64.7 +/- 18.5 [n = 9]; p less than 0.05). Prednisolone in the culture medium at physiologic concentrations suppressed the release of IL-1 and enhanced the release of IL-1 IHA. IL-1 IHA inhibited not only mouse thymocyte proliferation but also human fibroblast proliferation in the presence of IL-1.
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PMID:IL-1 and IL-1 inhibitory activity in the culture supernatants of alveolar macrophages from patients with interstitial lung diseases. 199 25

We have characterized antimyeloid monoclonal antibodies (mAbs) produced to human rheumatoid arthritis (RA) synovial tissue macrophages (MPs) (8D7) and to lipopolysaccharide (LPS)-treated U937 cells (3D8). The 3D8 antigen is upregulated with LPS stimulation of monocytes/MPs and during monocyte maturation. The 8D7 antigen is upregulated on functionally distinct subpopulations of RA synovial tissue MPs. We used immunohistochemistry to determine the spectrum of reactivity of these unique mAbs on myeloid cell suspensions, monocytes, and mature tissue inflammatory and noninflammatory MPs. The antigens identified by the mAbs were characterized biochemically, by immunoprecipitation of solubilized 125I-labelled antigens from cell surfaces, and immunohistochemically by enzymatic digestion of myeloid cells followed by a cellular ELISA. MAb 3D8, characterized as an anti-CD13 antibody, recognizes a 150-170 kd antigen, has almost exclusive myeloid reactivity, but reacts with Langerhans' cells of the skin and thymus, pointing to shared antigens between these cells and MPs. Unlike 3D8 antigen, 8D7 antigen is strongly expressed in inflammatory states, being present on MPs in granulomata as well as in sarcoid lymph nodes. Both mAbs react with frozen and methanol-Carnoy's fixed, paraffin-embedded tissues and detect antigenic differences among human mononuclear phagocytes present in different anatomical sites and in varying stages of differentiation and activation. These mAbs should prove to be a valuable tool for studying heterogenous populations of myeloid cells.
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PMID:Reactivity of human tissues with monoclonal antibodies to myeloid activation and differentiation antigens. An immunohistochemical study. 207 88

Interleukin-1 (IL-1), a modulatory protein with immune and inflammatory functions, is spontaneously released by tissue macrophages in lower concentrations compared with peripheral blood monocytes. Conversely, in idiopathic pulmonary fibrosis, sarcoidosis, and certain inflammatory diseases, increased amounts of IL-1 are released by alveolar macrophages (AM). We examined IL-1 production by AM from patients with adult respiratory distress syndrome (ARDS) and compared it with that in patients with severe pneumonia requiring assisted ventilation, patients with pneumonia requiring parenteral antibiotics, and healthy control subjects. In vitro, ARDS AM released significantly more total IL-1 and IL-1 beta than did ARDS AM in patients with pneumonia and in control subjects. Moreover, after stimulation of these cells with 10 micrograms/ml of lipopolysaccharide (LPS), ARDS AM significantly increased release of IL-1 and IL-1 beta. AM from patients with severe pneumonia also released greater amounts of both IL-1 and IL-1 beta as fresh explants and after LPS stimulation when compared with control subjects. Incubation of AM with 250 U/ml human interferon-gamma (gamma IFN) was associated with less IL-1 beta release. However, stimulating AM from patients with ARDS and severe pneumonia with gamma IFN plus LPS enhanced the release of IL-1 beta compared with that in patients with pneumonia and in control subjects. ARDS AM released significantly more IL-1 beta than did all of the other groups. These results demonstrate that AM from patients with ARDS are capable of releasing significantly greater amounts of IL-1, which may be related to the progression of acute lung injury.
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PMID:Elevated interleukin-1 release by human alveolar macrophages during the adult respiratory distress syndrome. 260 96

Regulation of the production of the biologically active vitamin D3 sterol 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] by cultured pulmonary alveolar macrophages (PAM) obtained from 6 patients with pulmonary sarcoidosis and from 9 normal subjects was studied. The sarcoid cells, all collected from patients with normal calcium metabolism, synthesized 1,25-(OH)2-[3H]D3 from the substrate 25-hydroxyvitamin [3H]D3 (25OH-[3H]D3), whereas in vitro incubation with recombinant human interferon-gamma (IFN gamma) or lipopolysaccharide (LPS) was required for induction of synthesis of the hormone by normal PAM. Exogenous 1,25-(OH)2D3 (10-100 nmol/L) decreased endogenous hormone production by normal PAM by approximately 45%. The relative inhibitory effect of 1,25-(OH)2D3 was less pronounced in sarcoid PAM, in which 10-100 nmol/L 1,25-(OH)2D3 inhibited 250HD3-1-hydroxylase by approximately 25%. An accompanying induction of the 250HD3-24-hydroxylase, which is typical for renal cells, was found at low levels in only 3 of 10 experiments; in this regard, no differences between sarcoid and normal PAM were apparent. PTH or forskolin did not influence 250HD3 metabolism by PAM. 1,25-(OH)2D3 production by sarcoid PAM was enhanced by lipopolysaccharide and IFN gamma. Likewise, recombinant human interleukin-2 stimulated 1,25-(OH)2D3 production by sarcoid PAM, suggesting a possible role for both IFN gamma and interleukin-2 in the induction of 1,25-(OH)2D3 synthesis by sarcoid PAM in vivo. Recombinant human IFN alpha, IFN beta, and granulocyte-macrophage colony-stimulating factor had little effect. Dexamethasone and chloroquine, which have in vivo antihypercalcemic activity in sarcoidosis, both inhibited 1,25-(OH)2D3 synthesis by sarcoid PAM; chloroquine simultaneously stimulated the 24-hydroxylase. Our studies suggest that the 250HD3-metabolizing system in PAM is in some respects different from renal metabolism of 250HD3.
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PMID:Regulation of 1,25-dihydroxyvitamin D3 production by cultured alveolar macrophages from normal human donors and from patients with pulmonary sarcoidosis. 311 53

To assess the ability of human alveolar macrophages to produce interleukin-1-beta (IL1-beta), we examined IL1-beta mRNA accumulation in autologous monocytes and alveolar macrophages from normal volunteers. Escherichia coli lipopolysaccharide stimulation of monocytes induced rapid IL1-beta mRNA accumulation, reaching a maximum at 2 to 4 h and declining thereafter. Alveolar macrophages, however, accumulated much less mRNA than did monocytes. This difference could not be explained by differences in kinetics of IL1-beta gene expression between the 2 cell types, isolation techniques, or alveolar macrophage lidocaine exposure. This suggests that differences in transcription of the IL1-beta gene exist between these 2 cell types. Aging is a possible factor important in some functional differences between these 2 cell types. To determine if this difference in the capacity to express the IL1-beta gene might be a function of cell maturity, monocytes were aged in vitro for 7 days. After this culture period, monocytes had a marked decrease in the ability to accumulate IL1-beta mRNA, suggesting that cell aging may be one mechanism involved in producing these transcriptional differences. Because IL1-beta has also been implicated in the inflammatory and fibrotic responses in pulmonary sarcoidosis, 4 patients with newly diagnosed sarcoidosis underwent bronchoalveolar lavage, and IL1-beta mRNA accumulation was compared in their alveolar macrophages and blood monocytes. Comparing normal alveolar macrophages to those from patients with sarcoidosis showed no differences in the kinetics of IL1-beta mRNA expression or in the LPS-induced levels of IL1-beta mRNA accumulation. In addition, augmented levels of IL1-beta transcript were not noted in unstimulated sarcoid alveolar macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-1-beta gene expression in human monocytes and alveolar macrophages from normal subjects and patients with sarcoidosis. 326 23

We have evaluated the hypothesis that the presence of large numbers of activated helper/inducer T lymphocytes in the lungs of individuals with active pulmonary sarcoidosis is associated with the exaggerated release of interleukin-1 (IL-1) by alveolar macrophages. Evaluation of media from unstimulated cultured sarcoid alveolar macrophages failed to detect IL-1 activity. When parallel cultures of sarcoid and normal alveolar macrophages were stimulated with lipopolysaccharide (LPS), they released similar amounts of IL-1 activity. Using a highly specific polyclonal anti-IL-1 beta antibody and flow cytometry to evaluate cell-associated IL-1 beta, analysis of fresh alveolar macrophages from patients with active sarcoidosis and normal individuals revealed no detectable cell-associated IL-1 beta, but IL-1 beta was present when macrophages from sarcoid patients and normals were stimulated with LPS. Similar observations were made using immunoblot analysis of cell lysates of the same unstimulated and stimulated macrophages. Finally, Northern analysis of alveolar macrophages for IL-1 beta mRNA transcripts demonstrated minimal, but equivalent, amounts of IL-1 beta in both normal and sarcoid macrophages, as compared to the much larger quantities present in LPS-stimulated alveolar macrophages. Thus, while alveolar macrophages of individuals with sarcoidosis are clearly capable of expressing the IL-1 beta gene, these findings suggest that altered expression of the IL-1 beta gene by alveolar macrophages does not play a central role in the exaggerated lung T-cell activation characteristic of sarcoidosis.
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PMID:Evaluation of alveolar macrophages in normals and individuals with active pulmonary sarcoidosis for the spontaneous expression of the interleukin-1 beta gene. 329 54

Interleukin 1 secretion from human alveolar macrophages was studied in patients with interstitial pulmonary fibrosis, sarcoidosis, and the acquired immunodeficiency syndrome with pneumonitis and compared to secretion from alveolar macrophages of normal volunteers. Macrophages lavaged from the lungs were stimulated with 10 micrograms/ml of lipopolysaccharide and cultured for 24 hr. In some cases macrophages were also stimulated with 1 microgram/ml lipopolysaccharide. After dialysis of the culture supernatants, interleukin 1 secretion was quantified by the thymocyte proliferation assay and probit analysis and expressed in terms of secretion from 1 million macrophages. Results showed that, on average, macrophages derived from patients secreted more interleukin 1 after stimulation with lipopolysaccharide compared to normal subjects. Mean secretion was significantly greater from macrophages of patients with acquired immunodeficiency syndrome and interstitial pulmonary fibrosis when stimulated with 10 micrograms/ml lipopolysaccharide. Of the 24 individuals studied, spontaneous interleukin 1 secretion was detected from unstimulated macrophages in only 1 patient and 1 normal volunteer. We conclude that alveolar macrophages lavaged from the lungs of patients with inflammatory lung disease have an increased capacity to secrete interleukin 1 on in vitro stimulation with lipopolysaccharide. Possible mechanisms for this increase are discussed.
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PMID:Interleukin 1 secretion from human alveolar macrophages in lung disease. 348 3

Human alveolar macrophages obtained from 7 normal volunteers and 7 patients with lung disease were stimulated with endotoxin (lipolysaccharide) to induce interleukin 1/leucocytic pyrogen (IL1/LP) secretion. Using the thymocyte assay we quantitated IL1/LP activity in macrophage supernatants obtained after 24 h. 10 micrograms/ml lipopolysaccharide stimulated alveolar macrophages to secrete significantly more IL1/LP activity than did 1 micrograms/ml. Apart from one patient with sarcoidosis, the presence of indomethacin did not significantly inhibit the quantity of IL1/LP secreted in response to LPS. We also demonstrated that the presence of indomethacin did not affect the response of thymocytes to IL1/LP. We conclude that the secretion of IL1/LP by human alveolar macrophages in response to endotoxin is not significantly reduced by the cyclooxygenase inhibitor indomethacin.
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PMID:Secretion of interleukin 1/leucocytic pyrogen from endotoxin-stimulated human alveolar macrophages is unaffected by indomethacin. 349 Apr 58


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