Possible role of LECT2 as an intrinsic regulatory factor in SEA-induced toxicity in d-galactosamine-sensitized mice.
To elucidate whether leukocyte cell-derived chemotaxin 2 (LECT2) controls the progression of staphylococcal enterotoxin A (SEA)-induced toxicity, we examined the role of LECT2 in a mouse model. Almost all the C57BL/6J (B6) mice survived for 72 h after the injection of 0.1 μg of SEA and 20 mg of d-galactosamine (d-GalN). However, the same treatment protocol in LECT2(-/-) mice produced a high lethality (~90%), severe hepatic apoptosis, and massive hepatic and pulmonary hemorrhage, similar to the situation observed in B6 mice treated with 1.0 μg SEA/d-GalN. The plasma LECT2 levels in B6 mice treated with 1.0 μg SEA/d-GalN were inversely correlated with the plasma cytokine levels and were associated with prognosis. LECT2 administration increased the survival of B6 mice and down-regulated TNF-α and IL-6. These results suggest the involvement of LECT2 in the regulation of fatal SEA-induced toxicity in d-GalN-sensitized mice.
Dang
Minh Hung
MH
Department of Microbiology and Immunology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Kato
Hidehito
H
Ueshiba
Hidehiro
H
Omori-Miyake
Miyuki
M
Yamagoe
Satoshi
S
Ando
Kazuyoshi
K
Imanishi
Ken'ichi
K
Arimura
Yutaka
Y
Haruta
Ikuko
I
Kotani
Tohru
T
Ozaki
Makoto
M
Suzuki
Kazuo
K
Uchiyama
Takehiko
T
Yagi
Junji
J
D000818:Animals; D017209:Apoptosis; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology / Q000633:toxicity; D005260:Female; D005434:Flow Cytometry; D005688:Galactosamine / Q000276:immunology*; D006470:Hemorrhage / Q000139:chemically induced; D020287:In Situ Nick-End Labeling; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012772:Shock, Septic / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004768:Enterotoxins; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; C491213:Lect2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C026066:enterotoxin A, Staphylococcal; D005688:Galactosamine