Inhibition of a membrane complement regulatory protein by a monoclonal antibody induces acute lethal shock in rats primed with lipopolysaccharide.
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.
Mizuno
M
M
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Nishikawa
K
K
Okada
N
N
Matsuo
S
S
Ito
K
K
Okada
H
H
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity*; D015703:Antigens, CD; D000954:Antigens, Surface; D001794:Blood Pressure / Q000276:immunology; D015936:Complement C5a / Q000378:metabolism; D003169:Complement Inactivator Proteins / Q000633:toxicity*; D003165:Complement System Proteins / Q000378:metabolism; D003520:Cyclophosphamide / Q000633:toxicity; D004546:Elapid Venoms / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007970:Leukopenia / Q000139:chemically induced / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology* / Q000633:toxicity; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044087:Receptor, Anaphylatoxin C5a; D011956:Receptors, Cell Surface; D011951:Receptors, Complement / Q000737:chemistry* / Q000276:immunology*; D012772:Shock, Septic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000954:Antigens, Surface; D003169:Complement Inactivator Proteins; C513105:Cr1l protein, rat; D004546:Elapid Venoms; D008070:Lipopolysaccharides; D044087:Receptor, Anaphylatoxin C5a; D011956:Receptors, Cell Surface; D011951:Receptors, Complement; C016310:cobra venom factor; D015936:Complement C5a; D003520:Cyclophosphamide; D003165:Complement System Proteins