Toxicity to alveolar macrophages in rats following parenteral injection of nickel chloride.
Alveolar macrophages collected by pulmonary lavage from male Fischer-344 rats at intervals (1-72 hr) after NiCl2 injection (62-500 mumol/kg, sc) were tested by several techniques. Within 1 to 4 hr, the macrophages showed morphological and biochemical signs of activation (hypertrophy, ruffled plasma membrane, increased cyclic AMP concentration, and markedly diminished 5'-nucleotidase activity, assayed by concanavalin A inhibition). Functional impairment (reduced phagocytic activity) was first seen at 24 hr; lipid peroxidation (increased malondialdehyde concentration) was not detected until 48 hr. Dose- and time-related effects of NiCl2 on 5'-nucleotidase activity, phagocytic activity, malondialdehyde concentration, and nickel content of alveolar macrophages were observed 24 to 72 hr postinjection. Diminished cell viability occurred only at 72 hr after the highest dosage of NiCl2. In alveolar macrophages from 63NiCl2-treated rats, 63Ni was located primarily in the cytoplasm, based upon liquid scintillation counting and autoradiography; fractionations of macrophage cytosol by gel filtration chromatography showed that 63Ni was bound to several high- and low-molecular-weight constituents. This study demonstrates that sc administration of NiCl2 to rats caused nickel uptake into and activation of alveolar macrophages, followed by reduced phagocytic capacity. The alveolar macrophage was a cellular target for nickel toxicity following parenteral exposure to NiCl2.
Sunderman
F W
FW
Department of Laboratory Medicine, University of Connecticut School of Medicine, Farmington 06032.
Hopfer
S M
SM
Lin
S M
SM
Plowman
M C
MC
Stojanovic
T
T
Wong
S H
SH
Zaharia
O
O
Ziebka
L
L
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D007279:Injections, Subcutaneous; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009532:Nickel / Q000378:metabolism / Q000633:toxicity*; D009708:Nucleotidases / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344
D008315:Malondialdehyde; C022838:nickel chloride; D009532:Nickel; D009708:Nucleotidases