Nanoscale transformations of amphiboles within human alveolar epithelial cells

Ruggero Vigliaturo,Magda Tušek Žnidarič,Giancarlo Della Ventura,Nada Žnidaršič,Günther J Redhammer,Goran Dražić,Reto Gieré,Simon Caserman,Maja Jamnik,Marjetka Podobnik

doi:10.1038/s41598-022-05802-x

Abstract

Amphibole asbestos is related to lung fibrosis and several types of lung tumors. The disease-triggering mechanisms still challenge our diagnostic capabilities and are still far from being fully understood. The literature focuses primarily on the role and formation of asbestos bodies in lung tissues, but there is a distinct lack of studies on amphibole particles that have been internalized by alveolar epithelial cells (AECs). These internalized particles may directly interact with the cell nucleus and the organelles, exerting a synergistic action with asbestos bodies (AB) from a different location. Here we document the near-atomic- to nano-scale transformations induced by, and taking place within, AECs of three distinct amphiboles (anthophyllite, grunerite, “amosite”) with different Fe-content and morphologic features. We show that: (i) an Fe-rich layer is formed on the internalized particles, (ii) particle grain boundaries are transformed abiotically by the internal chemical environment of AECs and/or by a biologically induced mineralization mechanism, (iii) the Fe-rich material produced on the particle surface does not contain large amounts of P, in stark contrast to extracellular ABs, and (iv) the iron in the Fe-rich layer is derived from the particle itself. Internalized particles and ABs follow two distinct formation mechanisms reaching different physicochemical end-states.

Highlights

Recording of mapping areas to obtain the chemical composition of a minimum of 100 particles
These amphibole particles may act as a source of reactive oxygen species (ROS)[25] in close contact with nuclei and cell organelles, and induce DNA damage in concert with the “external” action and stimuli triggered by asbestos[14,15,16,17,18,19,20], and the systemic response of the body to their presence
The results show that both composition and structure of the amphibole particles modified within AECs differ considerably from those of extracellular asbestos bodies (ABs), which have been described in some detail in the literature

Summary

Introduction

Recording of mapping areas to obtain the chemical composition of a minimum of 100 particles (dwell time 2 ms per pixel). This study focuses on the intracellular transformation of amphibole particles, and complements the extensive literature describing asbestos bodies (ABs), i.e., extracellular Fe-covered “fibers” found in lung tissue, and their role in triggering related malignancies. On the other hand, documents in unprecedented detail the transformation of micro- and nano-sized EMPs within AECs, using a unique set of transmission electron microscopy (TEM) techniques (Table 1). It provides unmatched information on the physicochemical end-states of internalized EMPs, which so far have not been reported in the literature. We further observed differences between transformations occurring in abiotic experiments and our in-vitro experiments, and we hypothesize that they can be related to the so-called “vital effect”

Methods

Results

Conclusion