Relationship between reduction of complement activation by polysaccharide surfaces bearing diethylaminoethyl groups and their degree of substitution.
The relationships between substitution of hydroxyl (OH) by diethylaminoethyl (DEAE) groups on cellulose membranes and the resulting reduction of complement activation are not clear. As a model, Sephadex has been randomly substituted with DEAE groups. Modification of 10% of the glucose units, i.e. about 3% of the groups, had no noticeable effect on the complement activating capacity of the polymer surface, whereas 20% substitution dramatically reduced it. This result could be explained in part by the fact that Sephadex-specific antibodies are not adsorbed by this modified surface. Thus, they cannot enhance complement activation as they do on Sephadex or cellulose. Comparison of our results with those published on Hemophan led us to the conclusion that a similar effect could occur. However, the degree of substitution of the membrane surface is probably greater than that of the membrane core due to the preparation process. Comparison with Sephadex substituted with other groups, or with other polymers bearing a variable density of OH groups, led us to the conclusion that, as hypothesized by Chenoweth (Artif Organs 1984; 8: 281-287), reduction of the availability of OH groups decreases complement activation, but the relationship is probably not linear. Moreover, replacement by other groups results in additional modulations due to (i) interactions between the groups and proteins responsible for formation or decay of the amplifying C3 convertase and/or (ii) decrease in recognition of the modified surface by antibodies which enhance complement activation on polysaccharides.
Laboratoire de Physico-Chimie, Pharmacotechnie, Biopharmacie, CNRS URA 1218, Université Paris Sud, Chatenay-Malabry, France.
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D000327:Adsorption; D000906:Antibodies / Q000494:pharmacology; D000918:Antibody Specificity; D003167:Complement Activation / Q000187:drug effects*; D015926:Complement C3a / Q000378:metabolism; D003637:DEAE-Dextran / Q000737:chemistry / Q000494:pharmacology*; D003911:Dextrans / Q000494:pharmacology*; D011134:Polysaccharides / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013499:Surface Properties
D000906:Antibodies; D003911:Dextrans; D011134:Polysaccharides; D015926:Complement C3a; C025614:sephadex; D003637:DEAE-Dextran