Publisher Summary This chapter discusses the chemical, physicochemical, and biological properties of mineral fibers. Among the most important occupational air pollutants are particles of coal, quartz, and fibers of asbestos, which are inhaled by miners and exposed industrial workers. Mineralogically, asbestos is divided into two classes: serpentine and amphibole. The former is a sheet silicate, whereas the latter is built up of double chains of tetrahedra. Chrysotile is the principal asbestos member of the serpentine family, whereas all other asbestos minerals belong to the amphibole group. Chrysotile asbestos is usually worked relatively near the surface by open-cast pit methods. Once the overburden has been cleared, explosives are used to release large tonnages of rock and fiber, the latter accounting for only a few percent of the parent rock. Crude asbestos, together with associated mother rock is conveyed to sorting stations, where waste rock is rejected and the ore undergoes a series of crushing and grinding operations. Fiber bundles of widely different lengths are inevitably mixed together. Subsequent screening results in a rough separation into grades but such screening is too imperfect to remove all the shorter fibers from the longer grades and even the lower grades contain a few long fibers.

Mineral Fibers: Chemical, Physicochemical, and Biological Properties

Mineral particles in the lung cause inflammation and silicosis. In myeloid and bronchial epithelial cells the inflammasome plays a role in responses to crystalline silica. Thioredoxin (TRX) and its inhibitory protein TRX-interacting protein link oxidative stress with inflammasome activation. We investigated inflammasome activation by crystalline silica polymorphs and modulation by TRX in vitro, as well as its localization and the importance of silica surface reactivity in rats. We exposed bronchial epithelial cells and differentiated macrophages to silica polymorphs quartz and cristobalite and measured caspase-1 activity as well as the release of IL-1β, bFGF and HMGB1; including after TRX overexpression or treatment with recombinant TRX. Rats were intratracheally instilled with vehicle control, Dorentruper quartz (DQ12) or DQ12 coated with polyvinylpyridine N-oxide. At days 3, 7, 28, 90, 180 and 360 five animals per treatment group were sacrificed. Hallmarks of silicosis were assessed with Haematoxylin-eosin and Sirius Red stainings. Caspase-1 activity in the bronchoalveolar lavage and caspase-1 and IL-1β localization in lung tissue were determined using Western blot and immunohistochemistry (IHC). Silica polymorphs triggered secretion of IL-1β, bFGF and HMGB1 in a surface reactivity dependent manner. Inflammasome readouts linked with caspase-1 enzymatic activity were attenuated by TRX overexpression or treatment. At day 3 and 7 increased caspase-1 activity was detected in BALF of the DQ12 group and increased levels of caspase-1 and IL-1β were observed with IHC in the DQ12 group compared to controls. DQ12 exposure revealed silicotic nodules at 180 and 360 days. Particle surface modification markedly attenuated the grade of inflammation and lymphocyte influx and attenuated the level of inflammasome activation, indicating that the development of silicosis and inflammasome activation is determined by crystalline silica surface reactivity. Our novel data indicate the pivotal role of surface reactivity of crystalline silica to activate the inflammasome in cultures of both epithelial cells and macrophages. Inhibitory capacity of the antioxidant TRX to inflammasome activation was evidenced. DQ12 quartz exposure induced acute and chronic functional activation of the inflammasome in the heterogeneous cell populations of the lung in associated with its crystalline surface reactivity.

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Silica-induced NLRP3 inflammasome activation in vitro and in rat lungs

Sirius Red staining is presented as a method for collagen determination, enabling quantitative morphometric measurements to be performed in locally defined tissue areas. The advantage of this method is especially shown for alveolar lung tissue. By excluding the bronchial areas in the tissue sections, the differences in the degree of fibrosis proved to be more discrete after different loads of quartz dust than by any other method. The difference of 12 micrograms collagen measured colorimetrically represented a 1.2-fold increase. The collagen measured in the alveolar tissue by the morphometric method rose from 9.8 to 28.6%. This is a 2.9-fold increase, underlining the vast improvement in sensitivity. Thus, this method is specifically suitable for the evaluation of very small fibrotic lesions. The quartz doses given are particularly low compared to most other investigations. Histologic lung and lymph node sections from female Wistar rats injected intratracheally with differing quantities of quartz dust (0.03, 0.1, 0.5, 1.75 mg) were stained with Sirius Red, and the collagen fibers measured with a quantitative image analysis. The results for lymph nodes using different methods (wet weight determination, quantitative measurement of quartz typical areas, colorimetric and morphometric collagen determination) showed a high correlation at the different doses. This showed that the morphometric method is suitable for the quantitative measurement of collagen. Corresponding results were also found in the comparative lung tissue measurements (colorimetric and morphometric collagen determination). However, the morphometric method has the decisive advantage that measurements can be restricted to defined tissue areas and do not destroy the section.

Advantages of Sirius Red Staining for Quantitative Morphometric Collagen Measurements in Lungs

Presented here is information on the mechanisms of action of different dusts and fibres of industrial interest. Emphasis is placed on the use of cell and organ culture, and lavage cell populations obtained from man and laboratory animals, in order to elucidate cellular and molecular events occurring after their interaction with fibrous and non-fibrous particulates, including metal compounds. In four sections, the volume provides research findings in the following areas: cellular and metabolic changes caused by mineral dusts; molecular changes and DNA alterations produced by mineral dusts; in vivo dust-related pathological processes; correlations between in vitro and in vivo data; and the physico-chemical properties of minerals in relation to their biological effects.

Cellular and Molecular Effects of Mineral and Synthetic Dusts and Fibres

Health economic loss measurement and risk assessment of new cases of coal worker’s pneumoconiosis in China

At first sight it appears paradoxical to study the etiology and pathogenesis of coal workers’ pneumoconiosis in animals by administering quartz dust and mixed dusts containing quartz intraperitoneally, rather than intratracheally or by inhalation. But, as revealed by our group, it is much easier to observe the typical tissue response to dusts in omentum and in lymph nodes than in the lungs. It will be demonstrated, on the basis of “short-term” and “long-term” experiments that the difference between the cell reactions to pure quartz and that to mixed dusts containing quartz is only a temporary one and that polyvinylpyridine-N-oxide (PVNO) modifies these reactions or prevents them from occurring. Part of the long-term experiments have been presented in earlier publications.o--R In this communication, further details of these experiments are reported.

W. Hilscher

Papers

Antagonistic factors in the pathogenesis of coal workers' pneumoconiosis