Non-Neoplastic and Neoplastic Pleural Endpoints Following Fiber Exposure

Abstract

Exposure to asbestos fibers is associated with non-neoplastic pleural diseases including plaques, fibrosis, and benign effusions, as well as with diffuse malignant pleural mesothelioma. Translocation and retention of fibers are fundamental processes in understanding the interactions between the dose and dimensions of fibers retained at this anatomic site and the subsequent pathological reactions. The initial interaction of fibers with target cells in the pleura has been studied in cellular models in vitro and in experimental studies in vivo. The proposed biological mechanisms responsible for non-neoplastic and neoplastic pleural diseases and the physical and chemical properties of asbestos fibers relevant to these mechanisms are critically reviewed. Understanding mechanisms of asbestos fiber toxicity may help us anticipate the problems from future exposures both to asbestos and to novel fibrous materials such as nanotubes. Gaps in our understanding have been outlined as guides for future research.

In vitro experimental models of mesothelioma revisited

“…Reliable inhalation studies with well-characterized aerosols of various asbestos fibers in long-term exposure animal models have not been reported due to cost, complexity, and lack of specialized instrumentation. Thus, few, if any, in vivo human mechanistic studies confirm the widely held concept of chronic inflammation associated with asbestos (27). Largely, it is indirect evidence that supports the pervasive role of inflammation in MPM pathogenesis.…”

“…The lymphatic network draining into stomata on parietal pleura has only been observed in small animal models, never conclusively demonstrated in humans (16,26). Additionally, there is virtually no knowledge about the kinetics of asbestos fiber translocation and deposition in human pleura (27); (II) While the majority of studies assume the cell of origin for MPM is the pleural mesothelial cell, a small body of literature theorizes other cell types could be responsible such as mesothelial progenitor cells that influx to parietal pleura or are induced in parietal regions of cellular damage caused by asbestos (5,28); (III) Related to this concept is the controversial field of cancer stem cell biology applied to solid tumors for which there is a paucity of literature to support this notion in MPM (29)(30)(31)(32). These reports are hampered by lack of a consistent and specific stem cell marker(s), and lack of reproducibility from serial dilution experiments of primary MPM samples; (IV) Although it is recognized that inflammation plays a role in MPM pathogenesis, the direct molecular mechanism(s), if any, linking inflammation to cancer development have not been described in detail.…”

Faserstäube, anorganisch [MAK Value Documentation in German language, 2018]

“…Es wird beobachtet, dass adsorbiertes Vitronectin (ein Se rumprotein) die Internalisierung über den Integrinα V β 5 Rezeptor erhöht. In ande ren Studien ist ermittelt worden, dass die internalisierten Asbestfasern von einem Marker für Endosomen und Phagosomen, der kleinen GTPase Rab5a, umschlossen sind (Broaddus et al 2011;Henry et al 2004;Nagai et al 2011). Diese Befunde ver deutlichen die Zellinternalisierung von Asbest via Endozytose.…”

“…verhinderte Phagozytose von persistenten Fasern kann dazu führen, dass diese fa serförmigen Partikel mit Alveolarzellen interagieren und mithilfe des Druckgradien ten durch die Pleuramembranen ins Interstitium transloziert werden. In der Pleura können Fasern durch direkte und indirekte Interaktionen mit den pleuralen Zellen Erkrankungen hervorrufen (Broaddus et al 2011). Wie Proteine, Zellen und Flüssig keiten werden auch körperfremde Partikel vom Pleuraraum durch lymphatische Stomata abtransportiert, welche sich zwischen den Mesothelzellen der parietalen Pleura öffnen (Broaddus et al 2011).…”

Gibt es Unterschiede in den gesundheitsschädlichen Wirkungen von Chrysotil- und Amphibol-Asbest?

“…Gleichzeitig fand sich eine Dominanz von Amphibolfasern im Lungengewebe [22]. Bisher wurden Faserbelastung und Fasertyp bei Patienten mit Pleuraerkrankungen nur vereinzelt untersucht, wobei Pleuraplaques in Zusammenhang mit langen Amphibol-und kurzen Chrysotilfasern festzustellen waren [64]. In einer aktuell veröffentlichten HRCT-Untersuchung wurde bei Automobil-Mechanikern, die gegenüber Chrysotil-haltigen Stäu-ben von Bremsbelägen und von Kupplungen exponiert waren und sonst keinen weiteren Asbest-Kontakt hatten, eine Prävalenz von Pleuraplaques von 4,9 % und von diffuser Pleuraverdickung von 3,9 % beobachtet [65].…”