The ability of Sephadex to activate human complement is suppressed in specifically substituted functional Sephadex derivatives.
The capacity of Sephadex and of chemically substituted Sephadex derivatives to activate human complement was examined by incubating polymer particles in normal human serum (NHS) under conditions that allow classical and/or alternative pathway activation, and by determining complement consumption or generation of C3a antigen in serum. Sephadex was found to activate complement in NHS, mainly through the alternative pathway. The complement-activating capacity of Sephadex was directly related to the surface area of polymer that could interact with serum. Substitution of hydroxyl groups of Sephadex with carboxymethyl (CM) groups suppressed the complement-activating capacity of the polymer in a dose-dependent fashion so that Sephadex bearing an average of one or more CM groups per saccharidic unit exhibited no complement-activating ability. Blocking of CM groups on CM sephadex with amide bonds did not restore a complement-activating capacity to the polymer, indicating that intact hydroxyl groups of the sugar units are required for complement activation by Sephadex. CM Sephadex was also found to adsorb C3adesArg which bound to the polymer with a calculated affinity of 1 x 10(6) l x M-1. Substitution of Sephadex with carboxymethyl and benzylamide sulphonate groups which confers to the polymer the capacity to catalyse thrombin inactivation on its surface also suppressed the complement-activating capacity of Sephadex. Sephadex derivatives that lack complement-activating properties and adsorb anaphylatoxins may provide useful models for the design of cellulosic membranes and biomaterials with blood compatible properties.
D001769:Blood; D003167:Complement Activation / Q000187:drug effects*; D003176:Complement C3 / Q000031:analogs & derivatives / Q000096:biosynthesis; D015926:Complement C3a / Q000031:analogs & derivatives*; D003911:Dextrans / Q000494:pharmacology*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D013329:Structure-Activity Relationship
D003176:Complement C3; D003911:Dextrans; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a; C025614:sephadex