Complement Activation Resulting from Blood-Material Interactions

Recently there has been a growing awareness of the importance of the interactions of the human complement system with biomaterials which largely stems from the understanding that complement-materials interactions may result in the production of inflammatory mediators, termed C3a and C5a anaphylatoxins, that can produce significant pathopysiologic alterations in the exposed patient. This presentation will review studies of complement activation produced by various hemodialysis membranes. our current data suggests that hemodialysis membranes may be roughly divided into three categories. The first type of membrane displays a high complement-activating potential as judged by measurements of C3a antigen levels produced during dialysis. These membranes also liberate sufficient quantities of C5a to induce both significant granulocytopenia and cardiopulmonary effects. The second group of membranes exhibits a moderate capacity to activate complement, with the amount of C3a antigen produced by these devices being about half that seen with the highly activating dialyzers. Dialyzers in this intermediate group produce only enough C5a to provoke a modest degree of leukopenia and they generally fail to induce cardiopulmonary manifestations. The third type of device fails to produce significant amounts of either free C3a or C5a and does not produce significant granulocytopenia. Factors that could affect the propensity of a material to activate complement include the density and type of surface nucleophiles, and the presence of surface dcarge which may facilitate the interaction of regulatory components and the adsorbtion of both active and bystander proteins.