Oxidant radical release by alveolar macrophages after cadmium chloride exposure in vitro.
Chronic exposure to cadmium can cause lung emphysema, the mechanism of which is unknown. Current concepts on the pathogenesis of emphysema largely emphasize the role of a protease-antiprotease imbalance. The aim of this work was to study the effects of cadmium on the regulation of antiprotease activity and the release of oxidant radicals from alveolar macrophages. Guinea pig alveolar macrophages (AM) were exposed overnight to cadmium chloride (CdCl2) in vitro. To define the cytolytic threshold dose, cell lysis was evaluated by trypan blue exclusion and lactate dehydrogenase release. Non-cytolytic concentrations were then used (0.1, 0.4 and 0.8 ppm) to simulate chronic exposure conditions. Overnight exposure to 0.1, 0.4 and 0.8 ppm CdCl2 decreased intracellular ATP (mean +/- SD: 91 +/- 8%, 72 +/- 7%, 50 +/- 8% of control cells, respectively), suggesting that even at non-cytolytic doses, Cd2+ can cause cell injury. The assessment of oxygen radical release from AM after overnight exposure to CdCl2 showed a dose-dependent decrease to 54.3 +/- 8.2%, 32.2 +/- 4.3% and 25 +/- 3% of control after exposure to 0.1, 0.4 and 0.8 ppm Cd2+, respectively. At non-cytolytic concentrations (0.1, 0.4 and 0.8 ppm) CdCl2 did not decrease alpha 1-proteinase inhibitor activity either in the absence of AM or in the presence of AM and myeloperoxidase. In conclusion, our in vitro results do not suggest that a protease-antiprotease imbalance is involved in the pathogenesis of cadmium-induced emphysema.(ABSTRACT TRUNCATED AT 250 WORDS)
Leduc
D
D
Department of Chest Medicine, Erasme University Hospital, Brussels, Belgium.
Gressier
B
B
Gosset
P
P
Lheureux
P
P
de Vuyst
P
P
Wallaert
B
B
Yernault
J C
JC
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D019256:Cadmium Chloride; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002712:Chlorides / Q000633:toxicity*; D006168:Guinea Pigs; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D013481:Superoxides / Q000378:metabolism*; D000515:alpha 1-Antitrypsin / Q000378:metabolism
D002712:Chlorides; D000515:alpha 1-Antitrypsin; D002104:Cadmium; D013481:Superoxides; D000255:Adenosine Triphosphate; D019256:Cadmium Chloride