Also, we observed X-Gal positive cells located within the
P10 alveoli, including developing secondary septae. Based on their location and
morphology at the resolution shown, these cells could potentially be alveolar
smooth muscle cells, alveolar myofibroblasts, microvascular pericytes, or
endothelial cells of capillaries (Fig. 2 F and G). We also noted the presence
of X-Gal positive mesenchymal cells of unknown identity underneath the airway
and throughout the lung tissue between blood vessels (Fig. 2H).
A membrane/sac that that protects the body's major internal organs and allows
them freedom of movement (for example, lung contractions). The mesothelium is
comprised of several regions, including the abdominal cavity (peritoneum), the
chest cavity (pleura), and pericardium (heart).
The emphasis on the parietal pleura as the site of retention and focus for the
long fibre dose has important implications for our understanding of the origins
of mesothelioma, a subject of considerable scientific and, arguably, even
greater medico-legal significance. Mesothelioma continues to be a global
problem due to ongoing exposure to fibres and as a legacy from past exposure to
asbestos, even in countries where asbestos is currently banned or has been regulated
out of use for decades . Lung tissue burdens of asbestos fibres have long been
used as an index of exposure, but the above discussion highlighting the
parietal pleura, not the lung tissue, as the site of origin of mesothelioma
calls into question the relevance of parenchymal lung fibre burdens as a
correlate of mesothelioma. The lung diseases caused by asbestos i.e. lung
cancer and asbestosis - may well be related to the lung parenchyma tissue
burdens, since one would reasonably look in the target tissue for the effective
dose. However the same logic would dictate that the effective dose for
mesothelioma, which arises in the parietal pleura, should be sought in that
tissue. In fact the parietal pleura fibre burden has been studied, but only
very occasionally; for example Dodson and Atkinson cite Sebastien as stating
that, for asbestos fibre burden "lung parenchymal retention is not a good
indicator of pleural retention: indeed, there was no relationship between
parenchymal and pleural concentrations". This would be predicted from the
arguments presented in this paper. Therefore, whilst the lung parenchyma is a
site of fibre accumulation that is likely related to exposure, the lung
parenchyma is not expected to focus the effective dose for mesothelioma in the
way that the parietal pleura does through its action as a kind of 'sieve' that
selectively retains long fibres.Even supposing the parietal pleura were to be
chosen as the tissue of choice for assessing effective dose of long fibre for
the mesothelioma hazard, a considerable problem is posed in sampling it for
fibre-burden analysis because of their small size and the heterogeneous
distribution of the stomata over the parietal pleura. Yet these are exactly the
sites that should be sampled in order to find the dose responsible for the
mesothelioma response or to sample the site of developing mesothelioma in order
to determine its molecular ontogeny. These 'hot-spots' of dose could not be
easily selected at autopsy by a pathologist unless they knew specifically where
to look and even then the diluting effect of non-stomatal tissue in the
immediate vicinity could easily confound any attempt to determine the specific
long fibre dose at the stomata.
Fibres found in digested human lung and visceral pleura at autopsy following
death from mesothelioma are often short but, as described below, these are not
the site to seek the effective fibre 'dose' for mesothelioma, since the
parietal pleura is the site of mesothelioma initiation. In fact the site where
the effective dose for long fibres is initially applied is the parietal
mesothelium, which has seldom been sampled for fibre burden or dimensions.
However, in several studies, fibres recovered from the parietal pleura have
also been found to be short . This may be explained by the fact that, as
described above, the location of the longer fibres is likely to be very focal,
at the stomata. When this area was specifically sampled in 14 patients
diagnosed with asbestos-associated diseases, including mesothelioma, much longer
fibres were found concentrated there .
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