# Mineral Fibres and Asbestos Bodies in Human Lung Tissue: A Case Study
## 3 Results and Discussion
### New Insights in the Mechanism of Formation of ABs  
Asbestos fibres that have managed to pass the upper respiratory system (the first defence mechanism of the body against alien particles) and have been deposited in the alveolar space promptly summon accumulation of phagocytic cells (e.g., macrophages) in charge of dissolution and clearance of the fibres. This second defence mechanism of the body against respirable particles is effective for small spherical objects but fails for longer asbestos fibres. When macrophages fail to completely internalise the longer fibres (frustrated phagocytosis), an inflammatory activity is prompted. This inflammatory activity can become chronic, because fibres can be biopersistent and resist reiterated attempts of phagocytosis. At this stage, the third defence mechanism of the body may take place as \"frustrated\" phagocytic cells promote isolation of the alien particles by encapsulating them inside theABs. However, only fibres with the Stanton-type size can effectively undergo this process, which is mediated by Fe [37; 53]. Iron can be released during the inflammatory activity, if present in specific lysosomes, and can contribute to the formation of homogeneous aggregates of iron hydroxide micelles (ferritin or hemosiderin) around the fibres [22; 37]. The coating process takes place only where the lysosomal contents (mainly acid hydrolases) are released and accumulate on the fibre surface [37]. Macrophages are supposed to cause a compartmentalised production of ABs, which results in the typical segmented structure [37]. The peculiar sub-spherical structure of ABs is due to the globular shape of ferroprotein complexes, such as ferritin and hemosiderin [42], i.e., an accumulation of spherical corpuscles (e.g., ferritin micelles) around a cylindrical solid, such as a fibre, generates a rounded coating (AB segments). As clearly demonstrated by in vitro and in vivo experiments [37; 60; 61], assuming that abiotic pathways are negligible, the coating process starts as a smooth layer of ferroproteins and later develops into the characteristic beaded structure. The difference in size of the ABs located along the fibre and that of the bulbous ABs at the tip of the fibre has never been considered to date. Time-lapse video microscopy of macrophage-asbestos fibre-binding events [62; 63] showed that the macrophages try to internalise the long fibres by preferentially starting from their terminations. Consequently, this portion of the fibre is subject to repeated coatings, leading to increased thickness. Previous studies also state that the pearl structure is the final step of the fibre-coating process [37; 58]. However, our observations show that mature ABs can eventually develop secondary coatings that tend to cover the previous, segmented ABs (Figure 9b-d). Figure 12 merges the findings of our study with the consolidated models from the literature [37; 60; 61] to update the mechanism of AB formation in the human lung. In the first stage of development, ABs appear like a smooth, corrugated coating of the fibre (Figures 8f and 12b). Compartmentalised production of ABs by macrophages then leads to the development of the typical segmented structure (Figures 8d and 12c). Mature ABs show the completely beaded shape (Figures 9e and 12d). During growth, the AB segments at the tip of the fibre incorporate adjacent units and increase in size (Figures 8e and 12d). After remaining in lung tissue for a long time, the ABs may develop multiple coatings (Figures 9b,d and 12e). This phenomenon occurs mostly at the tips of the fibre (Figures 9b and 12e). Despite the existence of a large body of literature data dealing directly or indirectly with ABs, the source of the Fe to prompt formation of ABs is still a matter of debate. STEM-EDX chemical mapping (Figure 6) shows that the Fe distribution in the amphib  
Figure 12: Graphical representation of development of an AB. Mineral fibre is light purple; AB is dark grey; secondary coatings are light grey.