Gadolinium induces macrophage apoptosis.
Gadolinium (Gd) suppresses reticuloendothelial functions in vivo by unknown mechanisms. In vitro exposure of rat alveolar macrophages to GdCl3.6H20 caused cell death, as measured by trypan blue permeability, in both dose- and time-dependent fashions. Even a 10-min exposure to Gd caused significant cell death by 24 h. The morphology of Gd-treated cells, pyknosis and karyorrhexis prior to loss of membrane integrity, suggested apoptosis. Upon flow cytometric examination, Gd-treated propidium iodide-excluding cells demonstrated light scatter changes characteristic of apoptotic cells (decreased forward and increased right angle scatter). Gel electrophoresis of DNA from Gd-treated macrophages clearly showed the ladder pattern unique to apoptotic cells. Electron-dense structures containing Gd were observed via electron spectroscopic imaging within phagosomes and also within nuclei (associated with condensed chromatin). Gadolinium, endocytosed by macrophages and distributed to nuclei, causes apoptosis of macrophages in vitro.
Mizgerd
J P
JP
Physiology Program, Harvard School of Public Health, Boston, MA 02115, USA.
Molina
R M
RM
Stearns
R C
RC
Brain
J D
JD
Warner
A E
AE
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis / Q000187:drug effects; D005434:Flow Cytometry; D005682:Gadolinium / Q000493:pharmacokinetics / Q000633:toxicity*; D007424:Intracellular Fluid / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley
D004247:DNA; D005682:Gadolinium