Increased oxidant resistance of alveolar macrophages isolated from rats repeatedly exposed to cadmium aerosols.
This study investigated potential mechanisms of oxidant resistance in alveolar macrophages (AM) isolated from Lewis rats exposed repeatedly to cadmium aerosols. Macrophages from Cd-adapted animals significantly greater resistance to oxidant-induced cytotoxicity than control cells when challenged with hydrogen peroxide in vitro. Elevations in glutathione peroxidase and glutathione reductase activities were associated with increased oxidant tolerance but catalase activity was unchanged. Metallothionein (MT) expression (protein and mRNA) was dramatically up-regulated in response to in vivo Cd exposure. A study using immunocytochemistry and in situ hybridization techniques revealed significantly heterogeneity in the expression of metallothionein by AMs. The percentage of AMs positive for MT (protein and mRNA) and the degree of MT expression within individual cells increased in response to additional Cd exposures. A putative state of activation was suggested by differences in size and number of inclusion bodies in macrophages from Cd-adapted animals and by secretion of a cytokine with interleukin-1-like characteristics. In summary, AMs from Cd-adapted animals are distinguished from control cells with respect to: (1) increased oxidant resistance, (2) secretion of cytokines, (3) elevations in enzymes associated with glutathione metabolism, and (4) up-regulation in metallothionein expression.
Hart
B A
BA
Department of Biochemistry, University of Vermont, Burlington 05405, USA
Gong
Q
Q
Eneman
J D
JD
Durieux-Lu
C C
CC
Kimberly
P
P
Hacker
M P
MP
D000336:Aerosols; D000818:Animals; D001483:Base Sequence; D001681:Biological Assay; D002104:Cadmium / Q000008:administration & dosage / Q000494:pharmacology*; D016923:Cell Death; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity*; D017403:In Situ Hybridization; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis / Q000235:genetics; D008969:Molecular Sequence Data; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew
D000336:Aerosols; D016207:Cytokines; D012333:RNA, Messenger; D002104:Cadmium; D008668:Metallothionein; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase