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Inhibition of a Membrane Complement Regulatory Protein by a Monoclonal Antibody Induces Acute Lethal Shock in Rats Primed with Lipopolysaccharide¹

Masashi Mizuno^*, Kazuhiro Nishikawa^*, Noriko Okada, Seiichi Matsuo^*, Kenichi Ito^* and Hidechika Okada^2,

^* Third Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan; and Department of Molecular Biology, Nagoya City University School of Medicine, Nagoya, Japan

Rats pretreated with traces of LPS developed acute fatal shock syndrome after i.v. administration of a mAb that inhibits the function of a membrane complement regulatory molecule. Such a shock was not observed after the administration of large amounts of LPS instead of the mAb following LPS pretreatment. The lethal response did not occur in rats depleted of either leukocytes or complement, and a C5a receptor antagonist was found to inhibit the reaction. Furthermore, LPS-treated rats did not suffer fatal shock following the injection of cobra venom factor, which activates complement in the fluid phase so extensively as to exhaust complement capacity. Therefore, complement activation on cell membranes is a requirement for this type of acute reaction.

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