Lead treatment in vitro at early developmental stage of bone marrow-derived macrophages enhances NO production through IL-1beta and IL-6 but not TNF-alpha.
Lead (Pb(2+)) is known to decrease or block nitric oxide (NO) production by mature macrophages (mphi). Bone marrow cells were treated with various doses of lead in vitro and the morphological and functional changes were observed. Bone marrow cells were treated with various doses of lead (1, 10, 20 and 50 microM) at the start of culture with mphi growth factor (CSF-1), and after 6-7 days of culture, the resultant mphi (bone marrow-derived mphi, BMDM) showed decreased NO production. Unexpectedly, BMDM from the lowest does of lead treatment (1.0 microM) showed increased NO production. The increased NO production was due to increased expression of the iNOS gene and concurrent enhanced transcript levels of proinflammatory cytokines such as IL-1beta and IL-6, but not TNF-alpha. Lead treatment on mature BMDM showed decreased NO production in a dose-dependent manner. These results suggest that a low dose of lead affects developmental characteristics of BMDM through different proinflammatory cytokines, and the lead effects on precursor cells of mphi and mature mphi are different.
Song
J S
JS
Laboratory of Experimental Animal Science, Division of Toxicology, Korea Research Institute of Chemical Technology, 100 Jang-Dong, Yusong-Ku, Taejon, 305-343, South Korea.
Sim
S Y
SY
Hong
D P
DP
Dal Rhee
S
S
Song
C W
CW
Han
S S
SS
Yang
S D
SD
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007854:Lead / Q000494:pharmacology* / Q000633:toxicity; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms
D016207:Cytokines; D007854:Lead; D009569:Nitric Oxide; C029891:lead chloride; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse