Involvement of Kupffer cells in lipopolysaccharide-induced rapid accumulation of platelets in the liver and the ensuing anaphylaxis-like shock in mice.
Intravenous injection of Klebsiella O3 lipopolysaccharide (LPS) into BALB/c mice induces an anaphylaxis-like shock within minutes. Using 5-hydroxytryptamine as a marker for platelets, we previously suggested that a rapid platelet accumulation in the liver and lung precedes the shock, and that a complement-dependent platelet-degradation is involved in the shock. Here, we examined (i) the effect of platelet-depletion (using an anti-platelet monoclonal antibody) on the shock and (ii) the contribution of macrophages to the platelet-accumulation in those organs. LPS-induced platelet-accumulations in the liver and lung were confirmed by immunostaining. In platelet-depleted mice, the shock was largely prevented. The number of F4/80-positive macrophages was much greater in liver than in lung, and the hepatic macrophages were largely lost in mice given clodronate-encapsulated liposomes. In mice treated with such liposomes, both the LPS-induced accumulation of platelets in the liver (but not in the lung) and the shock were largely prevented, and repopulation of hepatic macrophages restored these LPS-induced responses. These results suggest that (i) platelets are indeed involved in the shock, (ii) Kupffer cells mediate the hepatic platelet accumulation, and (iii) preventing this hepatic accumulation can largely prevent rapid shock being induced by LPS (at the dose used here).
Yamaguchi
Kouji
K
Department Oral and Maxillofacial Surgery, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Sendai 980-8575, Japan.
Yu
Zhiqian
Z
Kumamoto
Hiroyuki
H
Sugawara
Yumiko
Y
Kawamura
Hiroshi
H
Takada
Haruhiko
H
Yokochi
Takashi
T
Sugawara
Shunji
S
Endo
Yasuo
Y
D000707:Anaphylaxis; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000943:Antigens, Differentiation / Q000378:metabolism; D001792:Blood Platelets / Q000276:immunology*; D007728:Kupffer Cells / Q000166:cytology / Q000276:immunology*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology*; D008099:Liver / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000276:immunology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012701:Serotonin / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D008070:Lipopolysaccharides; C036763:monocyte-macrophage differentiation antigen; D012701:Serotonin