Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0037116 (silicosis)
 1,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibrogenic properties of two dusts of synthetic hydrated amorphous silicas, Ze-O-Sil (French production) and Arsil (Polish production) were studied. Experimental silicosis was induced by intratracheal administration to rats of a single dust dose (50 mg in 0.6 ml NaCl). Fibrogenic properties were tested 3, 6, 9 months after administration of the dust. X-ray diffraction and chemical tests did not reveal any form of crystalline. Si02 in the composition of the investigated dusts. The dusts tested as compared with quartz, were characterized by a great solubility up to 211 mg/l, which made the dust excretion from the lungs easy; after 6 month-experiment approximately 1.2 mg of Arsil dust and about 28 mg of quartz dust residue was found. Fibrogenic properties of Arsil dust, represented by wet lungs weight increase and hydroxyproline content in lungs, were more pronounced than those of Ze-O-Sil. Hydroxyproline content 3 months after administration of Arsil, Ze-O-Sil, TiO2 and weak quartz amounted to 7.3 mg, 5.1 mg, 3.8 mg and 6.0 mg, respectively. Histological and ultrastructural investigations demonstrated that disseminated, multifocal granulomas were the basic reaction to both dusts; no clear histological signs of cytolytic action on the cells of dust granulomas were found. In the lungs no silicotic nodules or degeneration of changes were revealed. Neither biochemical tests nor histological examinations revealed a progressive development of fibrous connective tissue. In result of the studies the authors suggest 2 mg/m3 as a MAC value for Arsil dust instead of 10 mg/m3--the value which has been hitherto used.
 ...
PMID:[Experimental silicosis. I. Fibrogenic effect of synthetic amorphous silica]. 70 91

The contribution of the type II pneumocyte to the pathogenesis of silicosis is largely unknown. Prominent features of silicosis are hyperplasia and hypertrophy of type II epithelial cells, often accompanied by phospholipid accumulation in the lung. The biologic regulation of these events is poorly understood. This study addresses the question of a direct effect of silica on type II pneumocytes, since direct contact of the inhaled silica dust can occur in vivo. Type II cells were isolated from fetal rat lungs and their epithelial specificity was verified. Experiments were performed on 2nd passage monolayers in 2% serum. Repair, replication, and growth activity was evaluated by the incorporation of [3H]thymidine. Cytotoxicity was measured by quantitating the release of [14C]adenine and expressed as a cytotoxicity index (CI). Type II cell proliferation and cytotoxicity were evaluated for the mineral dusts silica (SiO2), aluminum-treated silica (SiO2AlK), and titanium (TiO2). Of these mineral dusts, only low concentrations of silica increased type II cell [3H]thymidine incorporation (silica 2.5 micrograms/mL: 52% above control, P less than .05; silica 20 micrograms/mL: 57% above control, P less than .02). In addition, silica increased the cell number significantly, although to a lesser degree. Exposure of the type II epithelial cells to silica dust for 24 h resulted in dose-dependent cytotoxicity (silica 10 micrograms/mL, CI = 9.1%, P less than .0002; 250 micrograms/mL, CI = 45.1%, P less than .0001). SiO2Al completely suppressed these proliferation and cytotoxicity effects, which were then similar to those of the inert dust, TiO2. These data suggest that direct exposure and contact of the type II pneumocytes to low-dose silica dust initiated repair, replication, and growth activity, while exposure to higher silica concentrations resulted in marked cytotoxicity. Both the repair, replication, and growth and the cytotoxic responses of the type II epithelial cells to silica exposure are related to the surface properties of silica.
 ...
PMID:Silica exposure induces cytotoxicity and proliferative activity of type II pneumocytes. 131 66

Quartz but not titanium dioxide (TiO2) induced the production of reactive oxygen metabolites (ROM) by human monocyte-derived macrophages, as measured by lucigenin dependent chemiluminescence. Activation of the macrophages with BCG, bacterial lipopolysaccharide and macrophage-activating factor (MAF) caused a prominent increase of quartz-induced ROM production, MAF having the strongest effect. The activation did not affect the TiO2 responses to the same extent. Assuming that ROM have a role in the pathogenesis of silica-induced disease in man, we suggest that enhancement of quartz-induced production of ROM by activated pulmonary macrophages may at least partly explain the experimental and epidemiological data indicating that activation of the immune system during infection promotes the development of silicosis.
 ...
PMID:Quartz-induced production of reactive oxygen metabolites by activated human monocyte-derived macrophages. 222 36

The activation of collagen synthesis during development of silicotic fibrosis was studied in rats exposed, in dusting chambers, to respirable SiO2 for periods of 2, 4, 6 or 12 months. Control animals were exposed similarly to clean air or TiO2. Development of fibrosis was followed by histological examination, measurement of lung weight and determination of lung collagen content (as hydroxyproline). A steady increase in lung weight and collagen content together with changes in cellularity and metabolic activity of the lungs, as ascertained by chemical determination of DNA and RNA, were measured in the lungs of the SiO2-exposed animals. Hybridization of total lung RNA, extracted at each time point, with cDNA probes specific for type I and type III procollagen mRNA levels showed that the development of fibrosis was associated with increased levels, as compared to age matched controls, of pulmonary procollagen mRNAs. Interestingly, the highest levels of procollagen mRNAs were observed in young (pretreatment control) animals, suggesting that during pulmonary development collagen metabolism in lungs is even greater than during development of fibrosis. In rats exposed to SiO2 the increase in type III procollagen mRNA occurred earlier than the increase in type I procollagen mRNAs. These observations demonstrate both age-dependent and silicosis-related changes in pulmonary procollagen mRNA levels. The results suggest that development of silicosis is associated with an altered capacity of the lungs to regulate collagen accumulation.
 ...
PMID:Characterization of excessive collagen production during development of pulmonary fibrosis induced by chronic silica inhalation in rats. 247 54

The number of metastatic foci in silicotic mice is approximately 1.5-fold that in normal mice and in mice treated with TiO2 as inert particles. Expression of matrix metalloproteinases (MMPs) tissue inhibitors of metalloproteinases (TIMPs) and selectins was investigated in silicotic mice with lung tumor metastasis. Expression of MMP-9 and P-selectin mRNA, but not MMP-2 and E-selectin, increased significantly, showing decreases of the ratio of expression in TIMPs/MMP-9 in tumor-bearing silicotic mice compared with the tumor-bearing normal mice and mice treated with TiO2. Pretreatment with anti-P-selectin antibody inhibited number of metastatic foci significantly in silicotic mice, while pretreatment of animals with anti MMP-9 antibody showed slight decrease of metastatic foci. This evidence indicated that up-regulation of P-selectin expression contributed to enhanced rate of tumor metastasis in lung with silicosis.
 ...
PMID:Expression of matrix metalloproteinase, tissue inhibitors of metalloproteinase and adhesion molecules in silicotic mice with lung tumor metastasis. 1276 41

We compare the adsorption behavior of high density lipoproteins (HDL) and low density lipoproteins (LDL) on "fibrogenic" and "nonfibrogenic" mineral dusts. The adsorption tests with bovine lipoprotein concentrate and human serum produced the following results: 1) All seven examined fibrogenic dusts (SiO2 DQ12, SiO2 F600, silica, graphite, TiC, kaolin, talc) adsorbed significantly more high density lipoproteins (HDL), than the five examined nonfibrogenic (inert) dusts (TiO2, SnO2, Al2O3, Fe2O3, Fe3O4). This different behavior was particularly conspicuous in the presence of competing adsorbates (serum proteins). 2) In contrast, the adsorption of LDL did not correlate with the fibrogenicity of the mineral dusts. 3) The known silicosis-protective substance polyvinylpyridine-N-oxide inhibits the HDL adsorption of alpha-quartz. These results indicate that the adsorption of HDL could have a causal relationship with the triggering of a fibrotic reaction. The adsorption on the surface of fibrogenic dust particles provides an exceptional opportunity for the intake of HDL by macrophages. During the phagocytosis of the inhaled dust particles, the HDL adsorbed on the surface of the particles could be taken up by macrophages regardless of the receptor. There the HDL particles and/or compounds associated with them, such as lecithin-cholesterol-acyltransferase, could stimulate the macrophages to release fibrogenic mediators by some yet unknown mechanism.
 ...
PMID:Adsorption of lipoproteins onto mineral dust surfaces: a possible factor in the pathogenesis of particle-induced pulmonary fibrosis? 1632 Jun 25