EFFECT OF SUBSTITUTED DEXTRAN DERIVATIVE ON COMPLEMENT ACTIVATION IN-VIVO

A soluble dextran derivatized with carboxylic groups (73%) and benzyla mide sulphonate groups (15%), termed CMDBS 25, exhibited significant a nticomplementary activity in the absence of anticoagulant activity. Th e polysaccharide inhibited both classical and alternative pathway-depe ndent complement activation in human and rat serum in vitro. Simultane ous administration of CMDBS 25 (100 mg) and crushed Sephadex G25 (20 m g) into normal Lewis rats suppressed systematic complement consumption that was induced by Sephadex in the animals by 98% for 1 h. Two conse cutive injections of 100 mg of CMDBS at 1 h interval resulted in total suppression of systemic complement activation for 2 h and in 50% supp ression for an additional 2 h. Infusion of CMDBS alone was well tolera ted and had no effect on CH50 in serum in vivo. Our results demonstrat e that CMDBS 25 exhibits anticomplementary properties in vivo and sugg est that the polymer represents a potential therapeutic agent for path ological conditions associated with complement activation.