The interaction of asbestos and iron in lung tissue revealed by synchrotron-based scanning X-ray microscopy

Asbestos fibres are known as a potent carcinogen associated with malignant mesothelioma and lung cancer, but the reasons for their toxicity and carcinogenic mechanisms are still unclear. Most often, the toxicity is ascribed to the specific physico-chemical characteristics of asbestos and, in particular, to its ability to adsorb iron that may cause an alteration of iron homeostasis in the tissue.
Using a combination of advanced synchrotron-based X-ray imaging and micro-spectroscopic methods representative tissue samples from ten patients exposed to asbestos (from shipyard workers in Monfalcone) have been studied obtaining important correlative morphological and chemical information for the chemistry of asbestos body formation and other changes in the surrounding lung tissue that cannot be obtained using conventional techniques. The iron concentration, distribution and speciation in diseased human lungs, monitored for the first time thanks to the high elemental and chemical sensitivity of synchrotron XRF spectro-imaging and micro-XANES, have shed light on the iron mobilization during asbestos permanence in lung tissue. The Fe XRF maps clearly demonstrate how the asbestos fibres and the formed iron-rich bodies around them can cause high mobilization of iron into the surrounding cells (mainly alveolar macrophages) and tissue. The results suggest both, continuous deposition of Fe-containing species (ferritin) around the asbestos fibres and metal release due to asbestos body degradation.
As already reported in previous studies, along with iron other chemical elements participating in the formation of asbestos bodies are phosphorus, calcium and magnesium indicative for calcification process as well. Comparing the Fe and Ca maps (Figure 1) it is evident that Ca concentration in the body and in the vicinity is more evenly distributed, which is most likely a consequence of phagocytosis.
Here and in a previous study conducted at the TwinMic beamline of Elettra the presence of magnesium in the asbestos bodies and its surroundings has been demonstrated too.

Figure 1.Tissue with a phagocytated asbestos fibre.  X-ray microscopy absorption (a) image and the corresponding XRF Fe, Si, Ca and Mg XRF maps of an asbestos fibre phagocytated by lung macrophages (revealed by phase contrast image and Ca distribution). The Mg map was taken in the area indicated in red in panel a. Fe (displayed in logarithmic scale) partially co-localises with Ca, indicating different steps of a biomineralization process.

This indicates that, along with adsorption of iron-containing species, the first steps of interaction between the asbestos fibres and the tissue involve magnesium aggregation. In the following stages the bio-mineralization process continues most likely inside the macrophages, involving ferritin together with phosphate, calcium and magnesium.

Another novelty is the information obtained from the XANES results revealing the presence of two types of iron in the asbestos body: along with the expected trivalent (Fe3+) corresponding to ferritin standards for mineral form of ferrihydrite, sensible variable percentages of haematite have been detected as well. The data suggest that the haematite results from ferrihydrite (from ferritin) transformation occurring with time. This intriguing modification of iron chemistry during asbestos body permanence together with the demonstrated altered iron metabolism in lung should have real pathogenetic meaning with diagnostic and therapeutic potential.

This research was mainly conducted at the TwinMic beamline at the Elettra laboratory and at the ID21 beamline of the ESRF synchrotron facility (Grenoble, France) and was supervised by Lorella Pascolo, Clara Rizzardi and Mauro Melato, in collaboration with the Department of Anatomical Pathology of the Hospital of Monfalcone.


 

This research was conducted by the following research team:

  • Lorella Pascolo, Mauro Melato, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy
  • Alessandra Gianoncelli, Maya Kiskinova, Elettra-Sincrotrone Trieste S.C.p.A., Trieste, Italy
  • Giulia Schneider, Clara Rizzardi, Department of Anatomical Pathology, Department of Pathology and Forensic Medicine, University of Trieste, Trieste, Italy
  • Murielle Salomé, European Synchrotron Radiation Facility, Grenoble, France
  • Manuela Schneider, Unit of Pathology, ASS n. 2 ‘‘Isontina’’ Department of Anatomical Pathology, Hospital of Monfalcone, Monfalcone, Gorizia, Italy
  • Carla Calligaro, Servizio Diagnostica Veterinaria, University of Udine, Udine, Italy.

Contact person:
Alessandra Gianoncelli, email: alessandra.gianoncelli@elettra.eu

Reference

L. Pascolo, A. Gianoncelli, G. Schneider, M. Salomé, M. Schneider, C, Calligaro, M. Kiskinova, M. Melato, C, Rizzardi, C., Scientific Reports 3, 1123, (2013), doi: 10.1308/ srep01123.

Last Updated on Wednesday, 27 March 2013 09:55