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PubMed1997

Electron microscopic microanalysis of bronchoalveolar lavage: a way to identify exposure to silica and silicate dust.

OBJECTIVES: The diagnostic implications of finding non-fibrous inorganic particles in bronchoalveolar lavage (BAL) fluid has not been fully assessed. The aim of this study has been to measure the silica and non-fibrous silicates in BAL fluid from populations with different exposures to inorganic dust, and to find whether such measurement is useful for diagnostic purposes. MATERIALS AND METHODS: BAL samples from 19 subjects with only environmental exposure to inorganic dust (group A, mean (SD) age 50.7 (15.2)), 23 subjects with normal chest x ray films exposed to silica or silicates at work (group B, mean (SD) age 52.0 (12.4)), and 15 subjects with a previous diagnosis of silicosis (group C, mean (SD) age 68.0 (6.5)) were studied. Absolute and relative cell counts were found, and the samples were prepared for microanalysis by electron microscopy (EM). Firstly, semiquantitative x ray microanalysis was performed to find the level of silicon (Si) (peak/background Si) and this was followed by microanalysis of individual particles by EM. Variables related to the level of Si detected were assessed with multivariate analysis. RESULTS: Detected levels were higher in group B (2.09, 95% confidence interval (95% CI) 1.56 to 2.82) and C (1.50, 95% CI 1.07 to 2.12) than in group A (0.87, 95% CI 0.66 to 1.16) (P < 0.05, Dunett t test). A first multivariate analysis showed that exposure to silica or silicates was the only determinant of the level of Si expressed as log peak/background Si, when adjusted for age, sex, smoking habit, and cell count. A second multivariate analysis with microanalysis of individual particles as an independent variable showed the silica count to be the main predictor of detected concentration of Si. Silica and non-aluminium silicates together explain 55.5% (R2) of the variation in detected levels of Si. CONCLUSIONS: Detected levels of Si in BAL fluid depend on silica count and are higher in subjects with exposure to inorganic dust at work, but will not discriminate between exposed subjects with and without silicosis. Because semiquantitative x ray microanalysis does not accurately define exposure to non-silica inorganic particles, this measurement must be followed by EM microanalysis of individual particles in most cases, especially when exposure to silicates or metal dust is suspected.

Adult↗
PubMed2001

Exposure to silica and silicosis among tin miners in China: exposure-response analyses and risk assessment.

OBJECTIVES: To investigate the risk of silicosis among tin miners and to investigate the relation between silicosis and cumulative exposure to dust (Chinese total dust and respirable crystalline silica dust). METHODS: A cohort study of 3010 miners exposed to silica dust and employed for at least 1 year during 1960-5 in any of four Chinese tin mines was conducted. Historical total dust data from China were used to create a job exposure matrix for facility, job title, and calendar year. The total dust exposure data from China were converted to estimates of exposure to respirable crystalline silica for comparison with findings from other epidemiological studies of silicosis. Each worker's work history was abstracted from the complete employment records in mine files. Diagnoses of silicosis were based on 1986 Chinese pneumoconiosis Roentgen diagnostic criteria, which classified silicosis as stages I-III-similar to an International Labour Organisation (ILO) classification of 1/1 or greater. RESULTS: There were 1015 (33.7%) miners identified with silicosis, who had a mean age of 48.3 years, with a mean of 21.3 years after first exposure (equivalent to 11.0 net years in a dusty job). Among those who had silicosis, 684 miners (67.4%) developed silicosis after exposure ended (a mean of 3.7 years after). The risk of silicosis was strongly related to cumulative exposure to silica dust and was well fitted by the Weibull distribution, with the risk of silicosis less than 0.1% when the Chinese measure of cumulative exposure to total dust (CTD) was under 10 mg/m(3)-years (or 0.36 mg/m(3)-years of respirable crystalline silica), increasing to 68.7% when CTD exposure was 150 mg/m(3)-years (or 5.4 mg/m(3)-years of respirable crystalline silica). Latency period was not correlated to the risk of silicosis or cumulative dose of exposure. This study predicts about a 36% cumulative risk of silicosis for a 45 year lifetime exposure to these tin mine dusts at the CTD exposure standard of 2 mg/m(3), and a 55% risk at 45 years exposure to the current United States Occupational Safety and Health Administration and Mine Safety and Health Administration standards of 0.1 mg/m(3) 100% respirable crystalline silica dust. CONCLUSIONS: A clear exposure-response relation was detected for silicosis in Chinese tin miners. The study results were similar to most, but not all, findings from other large scale exposure-response studies.

Adult↗
PubMed1996

T lymphocytes and silica-induced pulmonary inflammation and fibrosis in mice.

BACKGROUND: Silica-induced pulmonary inflammation and fibrosis in animals provides a good model for chronic pulmonary inflammation and fibrosis. Although lymphocytes are implicated in the pathogenesis of pulmonary fibrosis, experimental models using silica-treated athymic nude mice have not been successful in showing the fibrogenic mechanism regulated by T cells. The aim of this study was to re-evaluate the role of T lymphocytes in the development of silicosis by comparing the response to silica administration of nude athymic mutants with that of euthymic animals. METHODS: Suspensions of silica particles were transnasally administered to nude athymic mice (Balb/c nu/nu) as well as to their euthymic littermates (Balb/c nu/+). The degree of pulmonary inflammation and fibrosis was assessed on days 14, 28, and 56 based upon histological observation, analysis of collagen deposition in the lungs, and analysis of the cellular constituent, protein, and phospholipid content in the bronchoalveolar lavage fluid. RESULTS: Histologically, athymic mice developed less severe interstitial pneumonitis than euthymic mice. In euthymic mice the lung hydroxyproline content increased with time after silica administration from 6.48 (0.38) micrograms hydroxyproline/mg dry lung weight on day 0 to 8.87 (0.41) micrograms/mg on day 56. A gradual increase in lung hydroxyproline content was also observed in athymic mice but the increase was significantly smaller than in euthymic mice (6.63 (0.43) micrograms/mg on day 0, 7.90 (0.19) micrograms/mg on day 56). Administration of silica resulted in an increase in the number of macrophages and neutrophils and in the total protein and phospholipid content of the bronchoalveolar lavage (BAL) fluid in both mouse strains. No significant difference was detected between athymic and euthymic mice in the numbers of macrophages, but the increase in neutrophils in the BAL fluid of athymic mice was significantly smaller than in euthymic mice on days 14 and 56. The total protein and phospholipid content of the BAL fluid from athymic mice was lower than that from euthymic mice. CONCLUSIONS: T lymphocytes appear to be involved in the pathogenesis of silica-induced pneumonitis. Since pulmonary fibrosis develops even in nude athymic mice, T cells do not seem to play a primary part in fibrogenic response but they regulate, at least to some extent, the response of inflammatory cells and fibrogenesis of the lung.

Animals↗
PubMed1999

Silica dust and lung cancer in the German stone, quarrying, and ceramics industries: results of a case-control study.

BACKGROUND: A work force based case-control study of lung cancer was performed in non-silicotic subjects exposed to crystalline silica to investigate the association between silica dust and lung cancer excluding the influence of silicosis. METHODS: Two hundred and forty seven patients with lung cancer and 795 control subjects were enrolled, all of whom had been employed in the German stone, quarrying, or ceramics industries. Smoking was used as a matching criterion. Exposure to silica was quantified by measurements, if available, or otherwise by industrial hygienists. Several indices (peak, average and cumulative exposure) were used to analyse the relationship between the level of exposure and risk of lung cancer as odds ratios (OR). RESULTS: The risk of lung cancer is associated with the year of and age at first exposure to silica, duration of exposure, and latency. All odds ratios were adjusted for these factors. Considering the peak exposure, the OR for workers exposed to high levels (>/=0.15 mg/m3 respirable silica dust which is the current occupational threshold value for Germany) compared with those exposed to low levels (<0.15 mg/m3) was 0.85 (95% CI 0.58 to 1. 25). For the time weighted average exposure the OR was 0.91 (95% CI 0.57 to 1.46). The OR for the cumulative exposure was 1.02 (95% CI 0. 67 to 1.55). No increase in risk was evident with increasing exposure. CONCLUSIONS: This study shows no association between exposure to crystalline silica and lung cancer. The exclusion of subjects with silicosis may have led to dilution with respect to the level of exposure and therefore reduced the power to detect a small risk. Alternatively, the risk of getting lung cancer may be restricted to subjects with silicosis and is not directly linked to silica dust.

Adult↗
PubMed2002

Activation of NF-kappaB-dependent gene expression by silica in lungs of luciferase reporter mice.

Occupational exposure to crystalline silica is associated with the development of pulmonary inflammation and silicosis, yet how silica initiates pulmonary fibrosis and which cell types are involved are unclear. In studies here, we hypothesized that silica particles interact initially with pulmonary epithelial cells and alveolar macrophages (AMs) to cause transcriptional activation of nuclear factor (NF)-kappaB-regulated genes encoding inflammatory cytokines. Exposure of NF-kappaB luciferase reporter mice intratracheally to silica or lipopolysaccharide (LPS), but not the nonfibrogenic particle titanium dioxide (TiO(2)), increased immunoreactivity of luciferase protein in bronchiolar epithelial cells and AMs. Ribonuclease protection assays revealed significant (P < or = 0.05) increases in mRNA levels of inducible nitric oxide synthase, tumor necrosis factor-alpha, macrophage inflammatory protein-2, macrophage chemotactic protein-1 (MCP-1), interferon-gamma, interleukin (IL)-6, and IL-12 in lung homogenates of reporter mice after exposures to silica or LPS. Immunoreactivity of MCP-1 in these animals was localized to AMs and epithelial cells. These data are the first to show activation of NF-kappaB in situ by fibrogenic particles in pulmonary epithelial cells and AMs. Increased expression of NF-kappaB-related inflammatory cytokines by these cell types, which first encounter silica after inhalation, may be critical to the initiation of silica-associated lung diseases, thus providing a rationale for focusing on NF-kappaB in preventive and therapeutic strategies.

Animals↗
PubMed1994

Fatty-acid synthase activity and mRNA level in hypertrophic type II cells from silica-treated rats.

Silica instillation causes a massive increase in lung surfactant. Two populations of type II pneumocytes can be isolated from rats administered silica by intratracheal injection: type IIA cells similar to type II cells from normal rats and type IIB cells, which are larger and contain elevated levels of surfactant protein A and phospholipid. Activities of choline-phosphate cytidylyltransferase, a rate-regulatory enzyme in phosphatidylcholine biosynthesis, and fatty-acid synthase (FAS) are increased in type IIB cells isolated from rats 14 days after silica injection. In the present study, we examined the increase in FAS and cytidylyltransferase activities in type IIB cells as a function of time after silica administration. FAS activity increased rapidly, was approximately threefold elevated 1 day after silica administration and has reached close to the maximum increase by 3 days. Cytidylyltransferase activity was not increased on day 1, was significantly increased on day 3 but was not maximally increased until day 7. Inhibition of de novo fatty-acid biosynthesis, by in vivo injection of hydroxycitric acid and inclusion of agaric acid in the type II cell culture medium, abolished the increase in cytidylyltransferase activity on day 3 but not FAS and had no effect on activities of two other enzymes of phospholipid synthesis. FAS mRNA levels were not increased in type IIB cells isolated 1-14 days after silica injection. These data show that the increase in FAS activity in type IIB cells is an early response to silica, that it mediates the increase in cytidylyltransferase activity, and that it is not due to enhanced FAS gene expression.

Animals↗
PubMed1997

Involvement of NF-kappaB in silica-induced cyclooxygenase II gene expression in rat alveolar macrophages.

The role of nuclear factor (NF)-kappaB transcription factor in silica-induced cyclooxygenase (COX) II gene expression was examined in the rat alveolar macrophage cell line NR8383. Our results indicate that NF-kappaB can be activated in this cell line by silica exposure. Suppression of NF-kappaB activation in these cells leads to an attenuation of COX II mRNA accumulation induced by silica. Using an electrophoretic mobility shift assay and a reporter gene assay, we provide evidence that at least two kappaB sites in the 5'-flanking region of the rat COX II gene are involved for silica-induced transcriptional control of the COX II gene. The first motif, -404 GGGGATTCCC -395, is absolutely conserved in sequence and is localized in a similar position among the COX II genes found in humans, rats, and mice. The second motif, -91 GGGGAAAGCC -82, was conserved only in the mouse and rat COX II genes in sequence and in location. Aspirin, a COX inhibitor, was shown to suppress silica-induced NF-kappaB activation. However, prostaglandin E2, one of the important downstream reaction products catalyzed by the COX enzyme, was also shown to attenuate silica-induced NF-kappaB activation by retarding the degradation of silica-induced inhibitor NF-kappaB. These results suggest that an interdependent regulation may exist between NF-kappaB activation and COX or its products.

Animals↗
PubMed1988

Divergent effects of silica on lymphocyte proliferation and immunoglobulin production.

Silicosis is an interstitial lung disorder that is frequently associated with hypergammaglobulinemia and increased numbers of lymphocytes at sites of disease. To determine the effect of silica on the generation of immunoglobulin-secreting cells, mononuclear cells were stimulated with antigens or mitogens and placed into 1) high-density cultures (2.5 X 10(6) cells/ml) that were not exposed to silica, in which pokeweed mitogen (PWM)-induced generation of immunoglobulin-secreting cells was suppressed by the presence of monocytes; or 2) low-density cultures (0.5 X 10(6) cells/ml) that were not exposed to silica, in which PWM-induced generation of immunoglobulin-secreting cells was not suppressed. Silica added to PWM-stimulated high-density cultures significantly increased the numbers of immunoglobulin-secreting cells. Silica also significantly increased the numbers of immunoglobulin-secreting cells in high-density cultures stimulated with purified protein derivative and tetanus toxoid and augmented the proliferation of phytohemagglutinin-stimulated mononuclear cells (P less than 0.05). In contrast to high-density cultures, silica added with PWM to low-density cultures reduced the numbers of immunoglobulin-secreting cells. These studies suggest that silica can have potent regulatory effects on various cellular immune processes that are relevant to the lung.

Cell Survival↗
PubMed1990

Silica directly increases permeability of alveolar epithelial cells.

Alveolar epithelial cell injury and increased alveolar-capillary membrane permeability are important features of acute silicosis. To determine whether silica particles contribute directly to this increased permeability, we measured paracellular permeability of rat alveolar epithelium after exposure to silica, in vitro, using markers of the extracellular space. Silica (Minusil) markedly increased permeability in a dose- and time-dependent manner. This was not the result of cytolytic injury, because lactate dehydrogenase release from monolayers exposed to silica was not increased. Pretreatment of the silica with serum, charged dextrans, or aluminum sulfate blocked the increase in permeability. Scanning electron microscopy demonstrated adherence of the silica to the surface of the alveolar epithelial cells. Thus silica can directly increase permeability of alveolar epithelium.

Alum Compounds↗
PubMed1998

Role of interleukin-10 in the lung response to silica in mice.

There is evidence that, following exposure to crystalline silica, the release of several proinflammatory cytokines contributes to the induction of unbalanced inflammatory reaction leading to lung fibrosis. We have examined the potential contribution of interleukin-10 (IL-10), an anti-inflammatory cytokine, in the development of silicosis. In a mouse model of inflammatory lung reaction induced by intratracheal instillation of silica (0.5 mg and 5 mg DQ12/mouse), the levels of IL-10 protein (determined by ELISA) both in cells obtained after bronchoalveolar lavage (BAL) and in lung tissue homogenates were significantly increased when compared with controls. After in vitro lipopolysaccharide (LPS) stimulation (1 microg/ml), BAL cells obtained from silica-treated animals produced significantly more IL-10 protein and mRNA than cells obtained from control animals. To examine the role of IL-10 in the lung reaction induced by silica, IL-10-deficient animals were instilled with 5 mg of silica. Twenty-four hours after treatment, the amplitude of the inflammatory response (lactate dehydrogenase [LDH], protein and number of inflammatory cells in BAL) was significantly greater in IL-10-deficient animals than in the wild type. In contrast, the fibrotic response, evaluated by measuring lung hydroxyproline content and by histopathologic analysis 30 days after silica, was significantly less important in IL-10-deficient than in wild-type mice. Together, these data suggest that increased IL-10 synthesis induced by silica can limit the amplitude of the inflammatory reaction, but also contributes to amplify the lung fibrotic response.

Animals↗
PubMed1990

Hypertrophic alveolar type II cells from silica-treated rats are committed to DNA synthesis in vitro.

Alveolar type II cell hyperplasia and hypertrophy are common reparative responses of the alveolar epithelium after silica-induced lung injury. We studied in vitro DNA synthesis in type II cells isolated after silica instillation in the rat to determine the proliferative potential of silica type II cells in primary culture and to correlate alveolar type II cell size with the level of in vitro DNA synthesis. To determine if the alveolar lining fluid is a source of growth factors that stimulate alveolar type II cell proliferation, we also examined the mitogenic effect of bronchoalveolar lavage fluid (BALF) from silica-treated rats on type II cells in primary culture. Alveolar type II cells were isolated from rats 1, 2, 3, and 4 wk after intratracheal silica instillation, cultured in DME supplemented with 10% fetal bovine serum, and labeled with [3H]thymidine from day 1 to day 3 in culture. DNA synthesis was determined by [3H]thymidine incorporation and autoradiographic labeling index. The level of thymidine incorporation increased progressively from 22.3 +/- 5.4 x 10(3) dpm/well 7 d after silica instillation to 34.4 +/- 5.0 x 10(3) dpm/well at 28 d. Type II cells isolated 14 d after silica instillation were separated into groups of increasing cell size by centrifugal elutriation. The plating efficiency and alveolar type II cell purity (greater than 88%) were the same in all groups of elutriated cells. The hypertrophic type II cells had a higher level of thymidine incorporation (22.0 +/- 2.8 x 10(3) dpm/well) than the normotrophic type II cells (11.1 +/- 0.7 x 10(3) dpm/well) [P less than 0.01]).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2006

Silica induces macrophage cytokines through phosphatidylcholine-specific phospholipase C with hydrogen peroxide.

Silica particle-associated inflammation is implicated in the genesis of several pulmonary diseases, including silicosis and lung cancer. In this study we investigated the role of phosphatidylcholine-specific phospholipase C (PC-PLC) in silica-stimulated induction of TNF-alpha and IL-1beta and how PC-PLC activity is regulated by silica in a rat alveolar macrophage model. We demonstrated that inhibition of PC-PLC, which was achieved with tricychodecan-9-yl-xanthate (D609), blocked the silica-stimulated induction of TNF-alpha and IL-1beta in alveolar macrophage, suggesting that PC-PLC is involved in the silica-associated inflammatory response. PC-PLC activity was increased significantly by silica exposure, and this could be inhibited by MnTBAP, which catalyzes both the dismutation of O2.- to O2 and H2O2 and the dismutation of H2O2 to O2 and H2O, revealing that PC-PLC activity is regulated in a redox-dependent manner. This is further confirmed by the finding that PC-PLC activity was increased by exogenous H2O2. The intracellular calcium chelator BAPTA blocked the H2O2-increased PC-PLC activity, while the calcium ionophore, A23187, enhanced PC-PLC activity. The data indicate that PC-PLC plays critical roles in the silica-associated inflammatory response and that PC-PLC is regulated through redox- and calcium-dependent manners in alveolar macrophages.

Animals↗
PubMed1997

Tuberculosis Mortality and Silica Exposure: A Case-Control Study Based on a National Mortality Database for the Years 1983-1992.

A case-control study (8,740 cases; 83,338 controls) was done to evaluate the association between potential occupational exposure to silica and risk of tuberculosis (TB) mortality, using the National Occupational Mortality Surveillance database for 1983-1992. Potential silica exposure was based on the decedent's usual industry and occupation. Assignment of potential exposure to silica was based on the entire range of industries and occupations. Odds ratios (ORs) for mortality from respiratory TB associated with potential high and intermediate exposures to silica were 1.30 (95% CI 1.14-1.48) and 1.07 (95% CI 0.77-1.47), respectively, adjusting for silicosis, other pneumoconioses, age, gender, race, socioeconomic status, and potential exposure to active TB. The elevated OR was seen in all subgroups: male, female, white, and black. The average age at death among respiratory TB cases with potential silica exposure was significantly younger by four years than that among cases without potential silica exposure. The findings suggest that potential occupational exposure to silica alone, in the absence of silicosis, is associated with respiratory TB mortality, with a dose-response relationship.

Journal Article↗
PubMed1994

Silica radical-induced DNA damage and lipid peroxidation.

In recent years, more attention has been given to the mechanism of disease induction caused by the surface properties of minerals. In this respect, specific research needs to be focused on the biologic interactions of oxygen radicals generated by mineral particles resulting in cell injury and DNA damage leading to fibrogenesis and carcinogenesis. In this investigation, we used electron spin resonance (ESR) and spin trapping to study oxygen radical generation from aqueous suspensions of freshly fractured crystalline silica. Hydroxyl radical (.OH), superoxide radical (O2.-) and singlet oxygen (1O2) were all detected. Superoxide dismutase (SOD) partially inhibited .OH yield, whereas catalase abolished .OH generation. H2O2 enhanced .OH generation while deferoxamine inhibited it, indicating that .OH is generated via a Haber-Weiss type reaction. These spin trapping measurements provide the first evidence that aqueous suspensions of silica particles generate O2.- and 1O2. Oxygen consumption measurements indicate that freshly fractured silica uses molecular oxygen to generate O2.- and 1O2. Electrophoretic assays of in vitro DNA strand breakages showed that freshly fractured silica induced DNA strand breakage, which was inhibited by catalase and enhanced by H2O2. In an argon atmosphere, DNA damage was suppressed, showing that molecular oxygen is required for the silica-induced DNA damage. Incubation of freshly fractured silica with linoleic acid generated linoleic acid-derived free radicals and caused dose-dependent lipid peroxidation as measured by ESR spin trapping and malondialdehyde formation. SOD, catalase, and sodium benzoate inhibited lipid peroxidation by 49, 52, and 75%, respectively, again showing the role of oxygen radicals in silica-induced lipid peroxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA Damage↗
PubMed1998

Enhancement of nitric oxide production by pulmonary cells following silica exposure.

In vivo exposure of rat lungs to crystalline silica either by intratracheal instillation or by inhalation results in an increase in mRNA levels for inducible nitric oxide synthase (iNOS) in bronchoalveolar lavage cells (BALC), elevated nitric oxide (.NO) production by BALC, and an increase in .NO-dependent chemiluminescence (CL) from alveolar macrophages (AM). Induction of iNOS message occurs in both AM and polymorphonuclear leukocytes (PMN) harvested from silica-exposed lungs but is not significantly elevated in lavaged lung tissue. In vitro exposure of AM to silica does not stimulate .NO production or enhance iNOS message. However, treatment of naive AM with conditioned media from BALC harvested from silica-exposed rats does increase iNOS message and .NO production by these AM. The potency of this conditioned medium is dependent on interaction between AM and PMN. In the rat model, a relationship exists between the ability of various dusts to cause PMN recruitment or protein leakage into the alveolar space and the induction of iNOS message in BALC, i.e., silica > coal mine dust > carbonyl iron > titanium dioxide. Similarly, a comparison of BALC from a healthy volunteer, a silica-exposed coal miner with a normal chest radiograph, and a silica-exposed coal miner with an abnormal chest radiograph shows a correlation between pathology and both the level of iNOS message in BALC and the magnitude of .NO-dependent CL from AM. These data suggest that .NO may play a role in silicosis and that human pulmonary phagocytes exhibit enhanced .NO production in response to an inflammatory insult.

Animals↗
PubMedDate not supplied

The effects of different silicas on arachidonic acid metabolism in alveolar macrophages.

Bovine alveolar macrophages (BAM) prelabeled with 3H-arachidonic acid (AA) were exposed in vitro to different doses of DQ-12, Minusil-5, and Sigma silicas, or carbonyl iron beads. Arachidonic acid metabolites released into the culture medium by BAM were identified and quantitated using high performance liquid chromatography (HPLC). Cytotoxicity was assessed by the release of lactate dehydrogenase (LDH). At doses of 0.1 or 0.25 mg of DQ-12 silica and of 0.25 or 0.5 mg of Minusil-5 and Sigma silica, the release of cyclooxygenase metabolites (TXB2, PGE2, PGF2, and HHT) comprised greater than 95% of the total released AA metabolites. Silica doses above 0.5 mg led to 5-lipoxygenase metabolite release (LTB4, its two nonenzymatic isomers, and 5-HETE). This shift to 5-lipoxygenase metabolite release paralleled increased cellular cytotoxicity and was observed for each of the silicas. In contrast to silica stimulation, carbonyl iron beads elicited only small quantities of cyclooxygenase metabolites, no 5-lipoxygenase metabolites, and showed little cytotoxicity toward BAM. The relative potency of each particulate for stimulating the release of AA metabolites and LDH was calculated with DQ-12 greater than Minusil-5 greater than Sigma much greater than carbonyl iron beads. Our results indicate that the cytotoxic and presumed fibrogenic potential of a silica may be correlated with the potency to stimulate the release of 5-lipoxygenase metabolites from AM.

Animals↗
PubMedDate not supplied

Enhanced clearance of silica from mouse lung after instillation of a leukocyte chemotactic factor.

It has been suggested that increased recruitment of phagocytes and subsequent clearance of particles may follow instillation of a leukocyte chemoattractant to lungs containing silica. The present study quantitated serially the silica content in alveolar spaces, in lung tissue and in hilar lymph nodes of mice that received 2 mg silica only, compared to a group that also received 100 micrograms intratracheal chemotactic factor N-formyl-L-methionyl-leucyl-phenylalanine (FMLP) at 2 and 3 weeks after silica. These mice showed a supplemental increase in alveolar macrophages and neutrophils, and an increase in silica was measured in lavaged cells and fluid soon after FMLP injection. At all times to 16 weeks, the silica content of lung tissue was significantly lower in mice that also received FMLP, and in this group, pulmonary fibrosis was much reduced, as shown morphologically and biochemically. In addition, there was reduced translocation of silica to lymph nodes in FMLP-treated mice. The results indicate that induction of a controlled inflammatory response in the alveoli at a time when particles are present in the pulmonary interstitium can accelerate clearance by increasing phagocyte traffic to the alveoli. The subsequent reduction in particle content of the lung is associated with a lower level of pulmonary fibrosis.

Animals↗
PubMed1994

[The effect of silica on the development of experimental Acanthamoeba meningoencephalitis with reference to the macrophage role in mice].

The role of macrophages was observed in intranasally infected C3H/HeJ mice with trophozoites (3 x 10(5)) of Acanthamoeba culbertsoni which was a kind of free-living amoebae inducing meningoencephalitis in human and experimental animals. The mortality was 60% in the group of intraperitoneally injected mice with silica (0.5 mg/0.5 ml). It was much higher than that of 10% in the group of amoeba infected mice without silica administration. The phagocytic index of peritoneal macrophages co-cultured with Toxoplasma gondii was estimated daily. In contrast to the control and amoeba infected group which didn't show significant fluctuation of the phagocytic indices, the silica administrated group revealed under 3% until day 3, and gradual increase up to 24.7% in day 5 which was same level of amoeba infected group without silica administration. The level of interleukin-1b (IL-1b) measured by ELISA was the highest in the amoeba infected group without silica injection and the lowest in the amoeba infected group with silica administration. In the test of the amoebicidal activity of mice peritoneal macrophages in vitro, silica administration revealed reducing effect on amoebicidal activity of macrophages. In conclusion, macrophages were proven to play a significant role in defense mechanism against the development of experimentally induced Acanthamoeba meningoencephalitis.

Acanthamoeba↗