Technical Report 122

Particle translocation

Although phagocytosis by macrophages is the dominant method of trapping and processing particles in the lung tissue, some particles may enter the interstitium by inefficient alveolar macrophages phagocytosis. Some studies indicate that particles pass directly from lung parenchyma into blood vessels (and lymphatics vessels) without being carried by mobile cells.

Early literature hypothesised that very small particles can migrate to perivascular and peribronchial positions passing directly from the lung tissue (Gross and Westrick 1954). Electron microscopic studies (Lauweryns et al, 1974) showed that carbon particles (25 nm diameter) are cleared from the lungs of rabbits via the lymphatics system, while ferritin molecules (10 nm diameter) are absorbed by blood capillaries and lymphatics. After their intratracheal administration and within 30 minutes, both types of particles had translocated to the interstitium and the lymph vessels. Studies in vitro by Pratten & Lloyd, 1986 reported that macrophages show a 70-fold slower rate of uptake for 30-nm particles compared to bigger >100 nm particles. The quantitative role of blood capillaries and lymphatics in alveolar clearance was evaluated (Meyer et al, 1969), and estimated that particle absorption via lymphatics tissues is about a 37-fold that of blood.

PSPs, ultrafine particles (UFPs) show a tendency to translocate outside the lung compared to larger (> 100 nm) particles, and their clearance and retention is through interstitialisation rather than the usual alveolar macrophage mediate clearance (Kreyling et al, 2000). Uptake by epithelial cells can be implied from studies in rats exposed to UF iridium (15 nm and 80 nm), where some particles escaped AM clearance by penetration through the lung epithelium into systemic circulation reaching extrapulmonary organs. Although the translocated fraction was very low in these organs (< 0.01), the 15 nm fraction was an order or magnitude larger compared to that of the 80 nm material indicating an inverse relationship between size and translocation potential (Kreyling et al, 2002).

Site of retention is also species dependent; in experiments conducted with diesel exhaust following chronic exposure (Nikula el al. 1997), rats tend to retain greater portions of UFP in the lumen of alveolar ducts and alveoli compared to cynomolgus monkeys and humans, who retain more material in the interstitium (Section 5.3.).

Translocation of inhaled UFP from lung deposition sites is of interest because of the hypothesis that translocated particles may pose adverse health effects to extra pulmonary organs. Because poorly soluble particles vary in size, composition and form, it is challenging to define a generic approach to study translocation of PSP to extra pulmonary sites after their deposition in the lung.

There are however some specific studies available which help illustrate the phenomenon of particle translocation from lung tissues to extra pulmonary organs described in the following: