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Prepublished online as a Blood First Edition Paper on July 12, 2002; DOI 10.1182/blood-2002-01-0252.
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Blood, 1 November 2002, Vol. 100, No. 9, pp. 3233-3239
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
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
From the Departments of Oral Microbiology and
Immunology and Pharmacology, Graduate School of Dentistry, Tohoku
University, Sendai, Japan; Department of Biochemistry, Fukushima
Medical University, Japan; and Department of Microbiology and
Immunology, Aichi Medical University, Japan.
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
Escherichia 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 2 recombinant LPSs each having an O-region (from O8 or O9) linked to
K-12 LPSexhibited 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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