The fate of instilled apoptotic macrophages in the lungs.
Mercer-RR; Scabilloni-J; Antonini-J; Castranova-V; Wang-L
Toxicologist 2004 Mar; 78(S-1):336-337
Our previous studies of particle exposures have implicated abnormal accumulations of apoptotic macrophages and apoptotic bodies in lung injury from high burdens of low toxicity particles and low burdens of highly toxic particles. To determine how the lungs process abnormal accumulations of apoptotic cells, we have used intratracheal instillation of apoptotic or normal macrophages from autologous donor rats. We characterized the fate of instilled apoptotic and normal macrophages by prelabeling the cells with UV fluorescent beads (0.5 micron, bright blue, polystyrene). One million labeled cells were instilled and the animals sacrificed at 4 hrs, 1 day, 1 week or 4 weeks after instillation. The right lung of each animal was lavaged with PBS and the left lung was inflation fixed with cryopreservative. Cytospins of lung lavage and cryosections of lung were stained for apoptotic cells with yellow-green fluorescence labeled nucleotides by terminal deoxytransferase (TdT). At 4 hours, 50% of the microsphere labeled, apoptotic cells which had been instilled were phagocytized. By 1 day, greater than 90% of the instilled apoptotic macrophages were phagocytized. There were no TdT positive nuclei in microsphere labeled cells at one week. No microsphere labeled, normal macrophages were found to be phagocytized at any time point. TdT positive cells in the lungs receiving normal macrophages was too low to quantify. The results demonstrate that instilled apoptotic macrophages are rapidly ingested and processed by resident alveolar macrophages while otherwise normal macrophages are not.
Lung-burden; Lung-disorders; Toxic-effects; Toxins; Laboratory-animals; Animals; Animal-studies; Nucleotides; Lung-function; Pulmonary-system-disorders; Respiratory-system-disorders
The Toxicologist. Society of Toxicology 43nd Annual Meeting and ToxExpo, March 21-25, 2004, Baltimore, Maryland