Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. A specific method is described for the measurement of angiotensin I converting enzyme activity in plasma with 125 I-labelled angiotensin I used as substrate. 2. Converting enzyme activity in plasma from fifteen normal subjects, eleven patients with sarcoidosis, twelve patients with chronic obstructive pulmonary disease and three patients with shock lung was assayed by this technique. 3. Patients with sarcoidosis had increased plasma converting enzyme activity whether or not they were receiving steroid therapy. 4. Patients with chronic obstructive pulmonary disease and shock lung had decreased plasma converting enzyme activity, but extent of conversion did not correlate with the severity of the lung disease. 5. Converting enzyme activity in normal plasma could be completely inhibited by addition of exogenous angiotensin I in 0.5-2.5x107 times physiological concentration. Twice as much exogenous angiotensin I was needed to inhibit conversion completely in plasma from patients with sarcoidosis; one tenth as much in chronic obstructive pulmonary disease. These results indicate that plasma has a high capacity for angiotensin I conversion even in patients with pulmonary parenchymal disease. 6. Results suggest that plasma converting enzyme activity may be a reflection of pulmonary conversion and can be altered by pulmonary disease. 7. Measurement of plasma converting enzyme activity may be useful in studies designed to characterize the regulatory role of converting enzyme in the renin-angiotensin system and in cardiovascular homeostasis.
Clin Sci Mol Med 1976 Dec
PMID:Altered angiotensin I conversion in pulmonary disease. 18 91

Because granulocyte colony-stimulating factor (G-CSF) is known to induce granulopoiesis and activate mature neutrophils, this factor could be important in determining the number and functional activity of neutrophils at sites of lung disease. The purpose of this study was to evaluate the ability of lung immune and inflammatory cells to produce G-CSF, and to seek evidence for the spontaneous production of this factor by cells recovered by lavage from controls and patients with lung diseases in which neutrophils may play a pathogenetic role. Lavage cells from controls produced little G-CSF spontaneously. Alveolar macrophages (AM), but not lymphocytes, produced large amounts following endotoxin stimulation. Lavage cells from patients with respiratory failure associated with bacterial pneumonia, but not those with respiratory failure from noninfectious causes, spontaneously released G-CSF (32 +/- 24 and less than 1 U/10(6) AM, respectively). Lavage cells from five of 15 patients with sarcoidosis and one of five patients with diffuse pulmonary fibrosis also spontaneously released G-CSF, which could not be explained by endotoxin exposure. The release of G-CSF by endotoxin-dependent and -independent mechanisms could play a role in the recruitment and activation of neutrophils in bacterial pneumonia and participate in the pathogenesis of some interstitial lung diseases.
Am J Respir Cell Mol Biol 1991 Feb
PMID:Spontaneous release of granulocyte colony-stimulating factor (G-CSF) by alveolar macrophages in the course of bacterial pneumonia and sarcoidosis: endotoxin-dependent and endotoxin-independent G-CSF release by cells recovered by bronchoalveolar lavage. 170 67

Although interleukin (IL)-2 may in part be responsible for lymphocyte accumulation to sites of active sarcoidosis, other cytokines that control such recruitment are not well characterized. Similarly, the pathogenic rationale for the ability of sarcoid macrophages to produce 1,25-dihydroxycholecalciferol (calcitriol) is not understood. We studied the release of chemokinetic lymphokines from human nylon wool-non-adherent tonsillar lymphocytes (HNTLs) employing a standard in vitro lymphocyte migration assay. If mitogen-stimulated HNTL supernatants were fractionated by high-performance liquid chromatography, five positive and one negative chemokinetic factors could be identified. The five lymphocyte chemoattractant factors (LCFs) ranged in mol wt from 5 to 35 kD and stimulated the in vitro migration of nonsensitized human lymphocytes by 200 to 500%. The LCFs appeared distinct from IL-2, IL-1, or gamma-interferon. Co-incubation of HNTLs with mitogen and 1 nM calcitriol prevented the production or release of two of the LCFs and significantly decreased the quantity of a third LCF. Calcitriol also resulted in the appearance of a second negative chemokinetic factor, lymphocyte migration inhibitory factor (LyMIF). Combined with our previous studies demonstrating that calcitriol interferes with IL-2-induced lymphocyte migration, these results provide a rationale for an anti-inflammatory role for calcitriol in sarcoidosis and other granulomatous disorders. These experiments also demonstrate that the control of lymphocyte recruitment to inflammatory foci is multifactorial.
Am J Respir Cell Mol Biol 1991 Jan
PMID:Lymphocyte chemokinetic factors derived from human tonsils: modulation by 1,25-dihydroxyvitamin D3 (calcitriol). 198 77

Alveolar macrophages have the ability to downregulate immune processes in vitro. We have recently suggested the presence of interleukin-1 (IL-1) inhibitors in the supernatants of human bronchoalveolar lavage cells from patients with idiopathic pulmonary fibrosis or sarcoidosis. In the present study, we further analyze the cellular origin and the biologic properties of a 20- to 25-kD IL-1 inhibitor spontaneously produced by cultured human alveolar macrophages (AM). The inhibitor blocks IL-1-induced prostaglandin E2 production by human fibroblasts and the IL-1-related increase of phytohemagglutinin-induced murine thymocyte proliferation. After rigorous IL-1 alpha and IL-1 beta depletion, supernatants of lung macrophages specifically block the binding of IL-1 to its receptor on the murine thymoma cell line EL4-6.1 in a dose-dependent manner. These results indicate that AM from both normal donors and patients produce a specific IL-1 inhibitor that may be of importance in protecting the alveolar environment from the deleterious effects of excessive IL-1 production.
Am J Respir Cell Mol Biol 1990 Oct
PMID:Characterization of a specific 20- to 25-kD interleukin-1 inhibitor from cultured human lung macrophages. 214 78

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.
Am J Respir Cell Mol Biol 1990 Sep
PMID:Expression of granulocyte-macrophage colony-stimulating factor mRNA by inflammatory cells in the sarcoid lung. 220 40

We obtained a series (12 clones) of hybridomas, which produce monoclonal antibodies (Mab) to 5 different epitopes of the angiotensin-converting enzyme (ACE) molecule. These antibodies may be used to (1) map antigenic structure of ACE, including the study of immunologic heterogeneity of ACE from different organs and tissues; (2) study the immunohistochemical distribution of ACE in human tissues, including the diagnosis of sarcoidosis; (3) develop an ACE immunoassay, and (4) prepare an immunosorbent for large-scale ACE isolation and for ACE-apheresis. One of the antibodies, 9B9, when injected into the circulation of rat and monkey, accumulated with high specificity in the lungs as compared with either normal mouse IgG or other organs and blood. The highly specific and nontoxic accumulation of Mab 9B9 suggests that it also may be used for gamma scintigraphy visualization of the pulmonary vascular bed, detection of lung injury and as a vector for targeted drug delivery to the lung.
J Mol Cell Cardiol 1989 Feb
PMID:Monoclonal antibodies to angiotensin-converting enzyme: a powerful tool for lung and vessel studies. 254 25

Examination of the sarcoid granuloma by electron microscopic and electron microscopic immunocytochemical techniques shows that the sarcoid macrophage giant cell is rich in lysozyme, present within the centre of the syncytium in dense granules approximately 200 nm in diameter. The ultrastructure of the syncytium is that of an actively secretory cell, suggesting that the sarcoid macrophage giant cell actively produces as well as stores lysozyme, rather than being a fusion product of mononuclear cells which produce lysozyme, or being a site of storage of ingested lysozyme.
Virchows Arch B Cell Pathol Incl Mol Pathol 1980
PMID:Sarcoid macrophage giant cells. Ultrastructure and lysozyme content. 610 21

Mononuclear cells from patients with sarcoidosis respond to Kveim tissue suspensions in vivo and from granulomas. We attempted to develop an in vitro Kveim test by adding Kveim material to monocytes and lymphocytes from patients with sarcoidosis and observing the cells in tissue culture. Sarcoid leukocytes were grown in culture with either Kveim suspensions (100 microgram/ml), control human spleen extract (100 microgram/ml) or no foreign antigen. After 7 to 9 days, we counted the number of cells adherent to glass, the number of cells with nucleoli, and the number of giant cells. Despite equal monocyte inocula, cultures of sarcoid leukocytes consistently had more cells adherent to glass than did cultures from normal donors regardless of whether Kveim, spleen, or no antigen was added to the cultures. There were no significant differences in giant cell formation or in the number of cells with nucleoli in the sarcoid compared with the control cultures.
Virchows Arch B Cell Pathol Incl Mol Pathol 1981
PMID:In vitro culture of leukocytes from patients with sarcoidosis: in search of an "in vitro Kveim test". 611 12

Asteroid bodies in multinucleate giant cells from sarcoid granulomas were investigated by immunofluorescence and electron microscopy. The following points have been established: 1. Asteroid bodies are made up of individual components of the so-called cytoskeleton, predominantly vimentin filaments. Microtubules are involved in smaller amounts in the formation of the asteroid bodies. 2. They arise within the area of the cytosphere. The body of the asteroid includes the centrioles while the arms of the asteroid usually extend into the Golgi area and occasionally up to the cell nuclei. 3. Asteroid bodies result from aggregation of the flexible filamentous and microtubular systems of the centrosphere. The processes of aggregation probably result from local fluid shifts and sol-gel transformations. 4. The stellate form of the aggregations is determined by the preexistent radial arrangement of the elements of the cytosphere. 5. The prevailing specific environment of the underlying granulomatous disease, together with the internal characteristics of the structure and function of the giant cells, in particular in states of exhaustion may play a part in their development.
Virchows Arch B Cell Pathol Incl Mol Pathol 1983
PMID:Immunofluorescence microscopic demonstration of vimentin filaments in asteroid bodies of sarcoidosis. A comparison with electron microscopic findings. 613 93

Sarcoidosis is characterized by the accumulation of activated lymphocytes in the lungs and other organs and by the spontaneous production of the active form of vitamin D, calcitriol. We hypothesized that calcitriol may modulate the responsiveness of human lymphocytes to the relevant biologic mediator, interleukin-2 (IL-2). After culture for 48 h with phytohemagglutinin, human peripheral blood lymphocytes migrated through nitrocellulose filters, secured in microchemotaxis chambers, in response to IL-2. When calcitriol at 1 nM was included in the cultures, the migratory response to IL-2 was completely abrogated. This inhibitory effect was seen despite the fact that cultured lymphocytes continued to express the IL-2 receptor and other activation markers. A similar but more rapid effect could be demonstrated by including calcitriol in the lower well during our 3-h chemokinesis assay. Calcitriol blocked IL-2-induced lymphocyte migration in a dose-dependent fashion. The synthetic noncalcemic vitamin D analogue MC 903 was equally effective in this assay. IL-2-induced migration could also be prevented by the protein kinase C inhibitor H-7, but calcitriol appeared to be at least 1,000 times more potent. Our studies suggest that calcitriol is a potent natural immunomodulator with rapid suppressive effects that may be mediated through protein kinase C. Synthetic analogues such as MC 903 may offer exciting therapeutic opportunities.
Am J Respir Cell Mol Biol 1995 Jun
PMID:Calcitriol and its synthetic analogue MC 903 inhibit the interleukin-2-induced migration of human lymphocytes. 776 30


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