Effect of substituted dextran derivative on complement activation in vivo.
A soluble dextran derivatized with carboxylic groups (73%) and benzylamide sulphonate groups (15%), termed CMDBS 25, exhibited significant anticomplementary activity in the absence of anticoagulant activity. The polysaccharide inhibited both classical and alternative pathway-dependent complement activation in human and rat serum in vitro. Simultaneous administration of CMDBS 25 (100 mg) and crushed Sephadex G25 (20 mg) into normal Lewis rats suppressed systematic complement consumption that was induced by Sephadex in the animals by 98% for 1 h. Two consecutive injections of 100 mg of CMDBS at 1 h interval resulted in total suppression of systemic complement activation for 2 h and in 50% suppression for an additional 2 h. Infusion of CMDBS alone was well tolerated and had no effect on CH50 in serum in vivo. Our results demonstrate that CMDBS 25 exhibits anticomplementary properties in vivo and suggest that the polymer represents a potential therapeutic agent for pathological conditions associated with complement activation.
Thomas
H
H
INSERM U28, Hôpital Broussais, Paris, France.
Maillet
F
F
Letourneur
D
D
Jozefonvicz
J
J
Kazatchkine
M D
MD
D000818:Animals; D001798:Blood Proteins / Q000187:drug effects / Q000378:metabolism; D002264:Carboxylic Acids / Q000737:chemistry; D003167:Complement Activation / Q000187:drug effects*; D003911:Dextrans / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D012756:Sheep; D013451:Sulfonic Acids / Q000737:chemistry
D001798:Blood Proteins; D002264:Carboxylic Acids; D003911:Dextrans; D013451:Sulfonic Acids