Kupffer cell-mediated cytotoxicity induced by lipopolysaccharide0111:B4 is greater in dogs than in rats and monkeys.
To clarify the mechanism of sensitivity to an endotoxin lipopolysaccharide LPS0111:B4, which causes severe liver injury in a variety of animals, we have developed an in vitro assay to measure Kupffer cell-mediated cytotoxicity in the human liver cell line, WRL68. This assay could detect the decrease in Kupffer cell activity induced by gadolinium chloride (GdCl3), which is an inhibitor in Kupffer cells. Among Kupffer cells derived from dogs, rats, and monkeys, LPS-activated canine Kupffer cells exhibited remarkably high cytotoxicity against WRL68 cells. This species difference is correlated with a species difference in the lethality of LPS0111:B4. Additionally, the conditioned medium of LPS-activated canine Kupffer cells was also cytotoxic to WRL68 cells. To identify the mediators of this cytotoxicity, we measured the accelerated release of interleukin-1 beta, and interleukin-6 from Kupffer cells on stimulation with LPS0111:B4. From the correlation of the response to LPS0111:B4, interleukin-1 beta and interleukin-6 are considered to be responsible for the canine Kupffer cell-mediated cytotoxicity of LPS0111:B4.
Hamano
Takako
T
Toxicology Laboratory, Mitsubishi Pharma Corporation, 100-5 Yana, Kisarazu-shi, Chiba 292-0812, Japan.
Tong
Vincent
V
Mutai
Mamoru
M
Hayashi
Masao
M
Tanaka
Eiji
E
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli; D005682:Gadolinium / Q000494:pharmacology; D000882:Haplorhini; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000166:cytology / Q000196:embryology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; C440499:lipopolysaccharide, Escherichia coli O111 B4; D005682:Gadolinium; D001973:Bromodeoxyuridine; C038958:gadolinium chloride