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Prepublished online as a Blood First Edition Paper on July 12, 2002; DOI 10.1182/blood-2002-01-0252.

Submitted January 31, 2002
Accepted June 6, 2002
LPS-induced platelet response and rapid shock in mice: contribution of O-antigen region of LPS and involvement of the lectin pathway of the complement system
Lijuan Zhao, Yuko Ohtaki, Kouji Yamaguchi, Misao Matsushita, Teizo Fujita, Takashi Yokochi, Haruhiko Takada, and Yasuo Endo*
Department of Oral Microbiology and Immunology, Tohoku University, Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan; Department of Pharmacology, Tohoku University, Graduate School of Dentistry, 4-1, Seiryo-machi, Aobaku, Sendai 980-8575, Japan
Department of Pharmacology, Tohoku University, Graduate School of Dentistry, 4-1, Seiryo-machi, Aobaku, Sendai 980-8575, Japan
Department of Biochemistry, Fukushima Medical University, Fukushima 960-1295, Japan
Department of Microbiology and Immunology, Aichi Medical University, Nagakute, Aichi 480-1195, Japan
Department of Oral Microbiology and Immunology, Tohoku University, Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
* Corresponding author; email: endo{at}pharmac.dent.tohoku.ac.jp.
Intravenous injection of a lipopolysaccharide (LPS) into mice induces a rapid accumulation of platelets in the lung and liver. When degradation of the accumulated platelets occurs, anaphylactoid shock follows rapidly, the severity of the shock paralleling the quantity of platelets accumulated in the lung. Here we examined the contributions made by LPS structure and the complement system to the platelet response to LPS. BALB/c mice were injected with an LPS from E. coli O8, O9, O111, or K-12, or from recombinant mutants of K-12. The O regions of the O8 and O9 LPSs consist of a mannose homopolysaccharide (MHP), while that of O111 consists of a heteropolysaccharide (not including mannose), and K-12 LPS lacks an O region. O111 LPS was devoid of the ability to induce the platelet response or shock, while the ability of K-12 LPS was weak. The two recombinant LPSs -- each having an O region (from O8 or O9) linked to K-12 LPS -- exhibited activities similar to or stronger than those of their original LPSs. Mannose-binding lectin (MBL) complexed with MBL-associated serine proteases (MASPs) bound strongly to LPSs containing MHP and caused C4 activation. Moreover, the abilities of these LPSs to activate the complement system corresponded well with their abilities to induce the platelet response and rapid shock. These results suggest that the structure of the O-antigen region is important for the platelet response to LPS, and that activation of the lectin pathway of the complement system is involved in this response.

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