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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

T lymphocytes and alveolar macrophages accumulating in the lower respiratory tract of patients with pulmonary sarcoidosis are known to be activated to produce several cytokines, presumably leading to granuloma formation within the lung. I hypothesized that these cells produce colony-stimulating factors (CSF), which have been shown to affect the proliferation and function of monocyte/macrophage-lineage cells. To test this hypothesis, I tried to detect mRNA encoding CSFs in cells obtained by bronchoalveolar lavage using a reverse transcription-polymerase chain reaction. Macrophage-CSF mRNA was detected in all subjects examined and interleukin 3 mRNA in none. Granulocyte-macrophage CSF (GM-CSF) mRNA was detected in 15 of 20 patients with pulmonary sarcoidosis, whereas it was detected in none of the farmer's lung disease patients and normal controls. The sarcoid patients whose BAL cells expressed GM-CSF mRNA had more active disease than those patients whose BAL cells did not, as judged from clinical and laboratory findings. These results indicate that GM-CSF produced by the inflammatory cells plays a substantial role in the formation or maintenance of the sarcoid lesion.
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PMID:[Expression of granulocyte-macrophage colony-stimulating factor mRNA by inflammatory cells in the sarcoid lung and its clinical significance]. 151 59

T lymphocytes and alveolar macrophages accumulating in the lower respiratory tract of patients with pulmonary sarcoidosis are known to be activated to produce several cytokines, presumably leading to granuloma formation within the lung. We hypothesized that these cells produce colony-stimulating factors (CSFs), which have been shown to affect the proliferation and function of monocyte-/macrophage-lineage cells. To test this hypothesis, we tried to detect mRNA encoding CSFs in cells obtained by bronchoalveolar lavage using a reverse transcription-polymerase chain reaction. Granulocyte-macrophage CSF (GM-CSF) mRNA was detected in five of six patients with pulmonary sarcoidosis, whereas it was detected in none of the five normal controls. Macrophage-CSF mRNA was detected in all subjects examined, and interleukin-3 mRNA in none. These results suggest some relation of GM-CSF to sarcoid lesion formation.
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PMID:Expression of granulocyte-macrophage colony-stimulating factor mRNA by inflammatory cells in the sarcoid lung. 220 40

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

We investigated surface antigens and spontaneous cytokine production of T cells from bronchoalveolar lavage fluid (BALF) and aqueous humor (AH) from pulmonary sarcoidosis patients for a better understanding of the role of T cells in granuloma formation. The levels of CD3, CD11b, and CD28 antigen expression on freshly isolated T cells in the BALF of patients were significantly lower than those in peripheral blood lymphocytes (PBL) of either sarcoidosis patients or healthy donors (HD). In contrast, the levels of CD80 (B7/B7-1) and CD86 (B70/B7-2) antigen expression were significantly higher on these T cells and alveolar macrophages in the BALF of patients. Fifty-three T cell clones (TCC) established from the BALF and AH of the three sarcoidosis patients displayed primarily either CD4+ CD11b+ CD28+ or CD4+ CD11b- CD28- phenotypes. Most (61-90%) of these TCC spontaneously produced greater amounts of IL-1 alpha, IL-10, tumour necrosis factor (TNF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) than did TCC from the PBL from sarcoidosis patients or HD (P < 0.05). Interferon-gamma (IFN-gamma), IL-6, and IL-2, but not IL-4, were also produced by 40-48% of these TCC. These results suggest that CD4+ T cells of the affected organs of sarcoidosis patients are activated and involved in the immunopathogenesis of sarcoidosis through production of various cytokines.
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PMID:Spontaneous production of various cytokines except IL-4 from CD4+ T cells in the affected organs of sarcoidosis patients. 758 98

Sarcoidosis is a systemic granulomatous disorder of unknown origin characterized by activated T-lymphocytes and macrophages. Macrophage/monocyte-derived cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) have been shown to be involved in the pathogenesis of sarcoidosis. Although the production of TNF-alpha and IL-1 by alveolar macrophages (AM) and peripheral monocytes (PM) in response to lipopolysaccharide (LPS) in sarcoidosis has been well demonstrated, the production of these cytokines in response to granulocyte-macrophage colony-stimulating factor (GM-CSF) has not been delineated. The present studies were designed to examine the regulatory effect of GM-CSF on TNF-alpha and IL-1 beta production by AM and PM from patients with pulmonary sarcoidosis. Amounts of TNF-alpha and IL-1 beta in the culture supernatants of unstimulated AM from patients with sarcoidosis were significantly higher than those from normal subjects, whereas, there was no difference in the amounts of TNF-alpha and IL-1 beta in the culture supernatants of PM between patients with sarcoidosis and normal subjects. The amounts of TNF-alpha and IL-1 beta in the culture supernatants of GM-CSF or LPS-stimulated AM and PM were significantly higher than those of similarly stimulated AM and PM from normal subjects. This hyperresponsiveness of AM and PM to GM-CSF in patients with sarcoidosis might be relevant to the pathogenesis of sarcoidosis.
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PMID:Effect of GM-CSF on TNF-alpha and IL-1-beta production by alveolar macrophages and peripheral blood monocytes from patients with sarcoidosis. 821 77

A central factor in the pathogenesis of inflammatory and fibrotic lung disease (adult respiratory distress syndrome, sarcoidosis, idiopathic pulmonary fibrosis) is the locally elevated number of alveolar macrophages (AM). An elevation in the production rate of AM, chemoattraction and differentiation of monocytes, or a diminution in the death rate might be underlying mechanisms. The aim of the present study was to investigate the modulatory role of endotoxin and cytokines on the death rate of human AM. Lipopolysaccharide (LPS) treatment resulted in a 4-fold increase (7.6 to 30.2%) of AM death. AM death was apoptotic as assessed by in situ DNA end labeling (ISDE), transmission electron microscopy, DNA gel electrophoresis, fluorometry of fragmented DNA, and an ELISA specific for histone-associated DNA fragments. Among the different bacterial cell wall components tested, LPS was the only inducer of apoptosis in human AM. None of the tested cytokines (interleukin-1 beta [IL-1 beta], IL-4, IL-6, IL-10, tumor necrosis factor-alpha [TNF-alpha], transforming growth factor-beta 2 [TGF-beta 2], interferon-gamma [IFN-gamma], macrophage colony-stimulating factor [M-CSF], granulocyte colony-stimulating factor [G-CSF], and granulocyte-macrophage colony-stimulating factor [GM-CSF]) was capable of enhancing the spontaneous rate of apoptosis. However, LPS-induced apoptosis was significantly enhanced by the macrophage-activating cytokine IFN-gamma, and reduced by the macrophage-deactivating cytokines IL-4, IL-10, and TGF-beta.
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PMID:Apoptosis in human alveolar macrophages is induced by endotoxin and is modulated by cytokines. 867 23

This study was designed to investigate the ability of bronchoalveolar and blood mononuclear cells to produce inflammatory mediators in vitro in pulmonary sarcoidosis. Seventeen patients with pulmonary sarcoidosis (stage I n = 8; stage II/III n = 9) and 10 normal controls were investigated. Bronchoalveolar and peripheral blood mononuclear cells were cultured in serum-free medium, without stimulant, for 24 h, and the supernatants analysed for concentrations of interleukin (IL)-1 beta (IL-1 beta), IL-2, IL-6, tumour necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-gamma (IFN-gamma) and neopterin. Bronchoalveolar lavage cells (BALC) of sarcoid patients released significantly higher amounts of TNF-alpha, IL-6, IFN-gamma and neopterin in comparison to normal controls. When smokers were excluded, there was also an increased release of IL-1 beta and GM-CSF. In the sarcoid group, the levels of IL-1 beta, IL-6, TNF-alpha and GM-CSF showed highly significant correlations between each other, but not with IL-2, IFN-gamma or neopterin. Sarcoid patients whose BALC released more TNF-alpha or GM-CSF had higher percentage counts of alveolar macrophages but fewer lavage lymphocytes. In sarcoid patients, peripheral blood mononuclear cells (PBMNC) also released higher amounts of IL-1 beta, TNF-alpha, IL-6 and GM-CSF but less neopterin than normal controls. Patients whose PBMNC produced more IL-1 beta, IL-6 and GM-CSF had higher absolute and relative lavage neutrophil counts. No relationships were observed between cytokine release and radiographic or physiological markers of disease severity. We conclude from this study that sarcoid inflammation is associated with an increased and concerted release of monocyte/macrophage-derived cytokines not only in the lung but also in the peripheral blood. We speculate that the lymphokines, IFN-gamma and IL-2, are not the primary triggers.
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PMID:Pulmonary sarcoidosis: patterns of cytokine release in vitro. 883 33

The aetiology of the peripheral anergy in sarcoidosis is unclear. To investigate this further we measured the serum levels of several factors important in different aspects of immune regulation to obtain a profile of those factors which promote and inhibit immune activation in sarcoidosis. Thirty-seven patients with sarcoidosis and 20 healthy controls of similar sex and age comprised the study group. Serum IL-10, interferon-gamma (IFN-gamma), soluble CD23 (sCD23), IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1beta and tumour necrosis factor-alpha (TNF-alpha) were measured using in-house ELISAs. Vitamin D3 was measured using a radioreceptor assay. Serum levels of sCD23 and IL-10 were significantly elevated in patients with sarcoidosis relative to controls (median 13.9 versus 9.5 arbitrary units/ml, P<0.01 for sCD23, and 9.6 versus 5.0 pg/ml, P<0.04 for IL-10). Regardless of steroid therapy or disease activity, serum levels of IFN-gamma, TNF-alpha, IL-1beta, GM-CSF and IL-8 were no different in patients with sarcoidosis and controls. Vitamin D3 levels were significantly higher in patients with sarcoidosis versus normal controls (medians 78.0 versus 56.0, P<0.001), active sarcoidosis (n = 20) versus inactive disease (n = 17) (medians 81.5 versus 66.0, P<0.03) and active sarcoidosis versus controls (medians 81.5 versus 56.0, P<0.0002). The levels were no different between patients with inactive sarcoidosis and controls. We suggest that IL-10 and vitamin D3 may contribute to the peripheral anergy in sarcoidosis. The elevated serum sCD23 suggests an increase in peripheral humoral immunity. Consistent with a quiescent peripheral immune system, factors capable of monocyte/macrophage activation (TNF-alpha, IFN-gamma, GM-CSF and IL-8) were not elevated in the peripheral circulation.
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PMID:An assessment of peripheral immunity in patients with sarcoidosis using measurements of serum vitamin D3, cytokines and soluble CD23. 935 40

Several cytokines are involved in the pathophysiology of sarcoidosis. Granulocyte-macrophage colony-stimulating factor (GM-CSF) may be one of these cytokines because its mRNA is expressed by inflammatory cells obtained from the sarcoid lung. We thus asked two questions. Is GM-CSF secreted by bronchoalveolar lavage (BAL) cells? What type of cells express GM-CSF? GM-CSF secreted by the cultured BAL cells from 19 untreated sarcoid patients was measured by an enzyme-linked immunosorbent assay. The individual cells expressing GM-CSF mRNA were identified by in situ hybridization in seven patients. Spontaneous release of GM-CSF by BAL cells was demonstrated in one patient. When stimulated, BAL cells secreted GM-CSF in all subjects studied. In situ hybridization with digoxigenin-labelled GM-CSF cRNA probe revealed that the positive cells were round in shape and larger than lymphocytes, but smaller than large alveolar macrophages that are often irregular in shape. These results strongly indicated that small alveolar macrophages secrete GM-CSF in the sarcoid lesion. This phenomenon may contribute to the enhanced immunological activities observed in sarcoidosis.
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PMID:Secretion of GM-CSF by inflammatory cells in the lung of patients with sarcoidosis. 1020 Oct 51

The purpose of this study was to evaluate the role of several eosinophil growth factors including interleukin (IL)-5, interleukin (IL)-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the pathogenesis of interstitial lung disease with eosinophilia. IL-5, IL-3 and GM-CSF in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA) in patients with eosinophilic pneumonia (EP), bronchiolitis obliterans organizing pneumonia (BOOP), idiopathic pulmonary fibrosis (IPF), sarcoidosis and healthy volunteers. IL-5 in BALF was high only in patients with EP. IL-3 in BALF was undetectable in the majority of patients with these diseases. GM-CSF in BALF was detectable in 30-67% of each group of patients. In patients with BOOP and IPF, the number of eosinophils in BALF was higher in patients with detectable GM-CSF than in patients in whom GM-CSF was below the detection limit. Eosinophil cationic protein (ECP) was detected in all patients with EP and some with BOOP and IPF. There was a significant correlation between ECP levels and percentage or number of eosinophils in BALF. The results suggest the possibility that interleukin 5 in eosinophilic pneumonia, and granulocyte-macrophage colony-stimulating factor in bronchiolitis obliterans organizing pneumonia and idiopathic pulmonary fibrosis may play important roles in eosinophil recruitment in the lung. Activation of eosinophils in the lung is likely to be induced by both interleukin 5 and granulocyte-macrophage colony-stimulating factor.
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PMID:Interleukin 5 and granulocyte-macrophage colony-stimulating factor levels in bronchoalveolar lavage fluid in interstitial lung disease. 1115 99


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