INFLAMMATORY RESPONSE OF THE LUNG TO TUNGSTEN PARTICLES - AN EXPERIMENTAL-STUDY IN MICE SUBMITTED TO INTRATRACHEAL INSTILLATION OF A CALCIUM TUNGSTATE POWDER
Mnd. Peao et al., INFLAMMATORY RESPONSE OF THE LUNG TO TUNGSTEN PARTICLES - AN EXPERIMENTAL-STUDY IN MICE SUBMITTED TO INTRATRACHEAL INSTILLATION OF A CALCIUM TUNGSTATE POWDER, Lung, 171(4), 1993, pp. 187-201
Tungsten has been implicated as a cause of a severe form of pneumoconi
osis in humans, the so-called ''hard metal'' lung disease. We have inv
estigated the effect of intratracheal instillation of a powder of calc
ium tungstate on the pulmonary tissue of CD-1 mice. The tungsten-induc
ed alterations were studied using 3 microanatomical methods: cytologic
study of exudates obtained by bronchoalveolar lavage (BAL); histologi
c examination of paraffin-embedded sections of the lung; and scanning
electron microscopic (SEM) examination of lung samples using x-ray mic
roanalysis to detect tungsten in situ. The animals were sacrificed 1,
3, 7, 14, and 21 days after a single intratracheal instillation of 250
mug calcium tungstate particles suspended in 100 mul of saline. We fo
und that the metal particles induced a marked inflammatory response in
the bronchoalveolar space characterized by a biphasic attraction of l
eukocytes with cellular peaks observed at day 1 and 14. More than 50%
of the BAL macrophages showed ingested tungsten. In the lung parenchym
a, the inflammatory-infiltrates were predominantly located at the peri
phery of the bronchiolar walls. From 7 days on after the tungsten depo
sition, large inflammatory exudates were seen invading focal areas of
the alveolar domain of the lung. SEM views revealed that the tungsten
particles could be inside alveolar macrophages, in cells making up the
alveolar wall, or inside periacinar lymphatics. Our data document tha
t tungsten particles cause a marked inflammatory response in the lung
tissue and that the leukocyte exudates may invade alveolar areas of th
e lung. This strong inflammatory response may correspond to the early
stages of the tungsten-induced '' hard-metal '' lung disease previousl
y reported in humans.