Mechanisms and Consequences of Complement Activation During Hemodialysis

  • Michel D. Kazatchkine
  • Nicole Haeffner-Cavaillon
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 260)


Activation of the complement system and secondary leukocyte activation mediate, both directly and indirectly, the acute and chronic effects resulting from immunological bioincompatibility of extracorporeal circuits. This manuscript briefly reviews the mechanisms and consequences of complement activation during hemodialysis. It focuses on recent studies from our laboratory suggesting a role for specific antibodies in the initiation of alternative pathway activation by cellulosic membranes, and indicating that circulating monocytes are stimulated to produce Interleukin-1 (IL-1) in vivo during bioincompatible hemodialysis.


Complement Activation Cellulosic Membrane Extracorporeal Circuit Polysulfone Membrane Alternative Pathway Activation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Arnaout, M.A., Hakim, R.M., Todd III, R.F., Dana, N., Colton, H.R.: Increased expression of an adhesionpromoting surface glycoprotein in the granulocytopenia of hemodialysis. New Engl. J. Med. 312:457 (1985).PubMedCrossRefGoogle Scholar
  2. 2.
    Bhakdi, S., Fassbender, W. , Hugo, F., Berstecher, C., Malasit, P., Carreno, M.P., Kazatchkine, M.D.: Relative inefficiency of terminal complement activation. J. Immunol. 144:3117 (1988).Google Scholar
  3. 3.
    Bingel, M., Lonnemann, G. Shaldon, S., Koch, K.M., Dinarello, C.A.: Human IL-1 production during hemodialysis. Nephron 43:161 (1986).PubMedCrossRefGoogle Scholar
  4. 4.
    Carreno, M.P., Labarre, D., Jozefowicz, M., Kazatchkine, M.D.: The ability of Sephadex to activate human complement is suppressed in specifically substituted functional Sephadex derivatives. Mol. Immunol. 25:165 (1988).PubMedCrossRefGoogle Scholar
  5. 5.
    Carreno, M.P., Maillet, F., Labarre, D., Jozefowicz, M., Kazatchkine, M.D.: Specific antibodies enhance Sephadexinduced activation of the alternative complement pathway in human serum. Biomaterials 9:514 (1988).PubMedCrossRefGoogle Scholar
  6. 6.
    Carreno, M.P., Labarre, D. Jozefowicz, M., Kazatchkine, M.D.: Regulation of the human alternative complement pathway: formation of a ternary complex between Factor H, surface-bound C3b and chemical groups on nonactivation surfaces. Submitted.Google Scholar
  7. 7.
    Chenoweth, D.E., Cheung, A.K., Ward, D.M., Henderson, L.W.: Anaphylatoxin formation during hemodialysis: effects of different dialyzer membranes. Kidney Int. 24:764 (1983).PubMedCrossRefGoogle Scholar
  8. 8.
    Chenoweth, D.E., Cheung, A.K., Ward., D.M., Henderson, L.W.: Anaphylotoxin formation during hemodialysis: comparison of new and re-used dialyzers. Kidney Int. 24:770 (1983).PubMedCrossRefGoogle Scholar
  9. 9.
    Chenoweth, D.E.: Complement activation during hemodialysis: clinical observations, proposed mechanisms and theoretical implications. Artif. Organs. 8:281 (1984).PubMedCrossRefGoogle Scholar
  10. 10.
    Cheung, A.K., Lewinter, M., Chenoweth, D.E., Lew, Y.W., Henderson, L.W.: Cardiopulmonary effects of cuprophanactivated plasma in the Swine: role of complement products. Kidney Int. 29:799 (1986).PubMedCrossRefGoogle Scholar
  11. 11.
    Cheung, A.K., Parker, C.J., Janatova, J.: Analysis of the complement C3 fragments associated with hemodialysis membranes. Kidney Int. 35:576 (1989).PubMedCrossRefGoogle Scholar
  12. 12.
    Craddock, P.R., Fehr, J., Birgham, K.L., Kronenberg, R.S., Jacob, H.S.: Complement and leukocyte-mediated pulmonary dysfunction in hemodialysis. New Engl. J. Med. 296:769 (1977).PubMedCrossRefGoogle Scholar
  13. 13.
    Dinarello, CA., Wolff, S.M.: Molecular basis of fever in humans. Am. J. Med. 72:799 (1982) .PubMedCrossRefGoogle Scholar
  14. 14.
    Dinarello, C.A.: Interleukin-1 and the pathogenesis of the acute phase response. New Engl. J. Med. 311:1413 (1984) .PubMedCrossRefGoogle Scholar
  15. 15.
    Durum, S.K., Schmidt, J.A., Oppenheim, J.J.: Interleukin-1: an immunological perspective. Ann. Rev. Immunol. 3:263 (1985).CrossRefGoogle Scholar
  16. 16.
    Haeffner-Cavaillon, N., Cavaillon, J.M., Moreau, M., Szabo, L.: Interleukin-1 secretion by human monocytes stimulated by the isolated polysaccharide region of the Bordetella pertusis endotoxin. Mol. Immunol. 21:389 (1984) .PubMedCrossRefGoogle Scholar
  17. 17.
    Haeffner-Cavaillon, N., Cavaillon, J.M., Cianconi, C., Bade, F., Delons, S., Kazatchkine, M.D. : C3a (C3ades-Arg) induces production and release of interleukin-1 by cultured monocytes. J. Immunol. 139:794 (1987).PubMedGoogle Scholar
  18. 18.
    Haeffner-Cavaillon, N. , Cavaillon, J.M. , Cianconi, C., Bacle, F., Delons, S., Kazatchkine, M.D.: In vivo induction of interleukin-1 production during hemodialysis. Kidney Int. 1989 in press.Google Scholar
  19. 19.
    Hakim, R.M., Lowrie, E.G.: Effect of dialyzer reuse on leukopenia, hypoxemia and total hemolytic complement system. Trans. Am. Soc. Artif. Organs 26:159 (1980).Google Scholar
  20. 20.
    Hakim, R.M., Breillat, J., Lazarus, J.M., Port, F.K.: Complement activation and hypersensitivity reactions to dialysis membranes. New Engl. J. Med. 311:878 (1984).PubMedCrossRefGoogle Scholar
  21. 21.
    Hazuda, D.J., La, J.C, Yound, P.R.: The kinetics of interleukin-1 secretion form activated monocytes. J. Biol. Chem. 263:473 (1988).Google Scholar
  22. 22.
    Henderson, L.W.: Symptomatic hypotension during hemodialysis. Kidney Int. 17:571 (1980).PubMedCrossRefGoogle Scholar
  23. 23.
    Henderson, L.W., Koch, K.M., Dinarello, C.A., Shaldon,S.: Hemodialysis hypotension the hypothesis. Blood Purif. 1:3 (1983) .CrossRefGoogle Scholar
  24. 24.
    Kazatchkine, M.D., Nydegger, U.E.: The human alternative complement pathway: biology and immunopathology of activation and regulation. Prog. Allergy 30:193 (1982).PubMedGoogle Scholar
  25. 25.
    Moore, F.D., Fearon, D.T., Austen, K.F.: IgG on mouse erythrocytes arguments activation of the human alternative complement pathway by enhancing deposition of C3b. J. Immunol. 126:1805 (1981).PubMedGoogle Scholar
  26. 26.
    Pangburn, M.K.: Mechanisms of recognition of alternative pathway activators: analysis using C3b-bound lowmolecular weight polysaccharides of defined structure. Complement (abstract) 4:208 (1987).Google Scholar
  27. 27.
    Petersen, M.J., Boyer, K.M., Carson, L.A., Favero, M.S.: Pyrogenic reactions from inadequate desinfection of a dialysis fluid distribution system. Dialysis Transplant. 7:52 (1978).Google Scholar
  28. 28.
    Port, F.K., Berkick, J.J.: Pyrogen and endotoxin reactions during hemodialysis. Contrib. Nephrol. 36:100 (1983) .PubMedGoogle Scholar
  29. 29.
    Ramadoni, G. , Sije, J.D. , Dinarello, CA.: Pretranslational modulation of acute phase hepatic synthesis by murine recombinant IL-1 and purified human IL-1. J. Exp. Med. 162:930 (1985).CrossRefGoogle Scholar
  30. 30.
    Robinson, P.J.A., Rosen, S.M.: Pyrexial reactions during hemodialysis. Br. Med. J. 1:528 (1971).PubMedCrossRefGoogle Scholar
  31. 31.
    Schenkein, H.A., Ruddy, S.: The role of immunoglobulins in alternative pathway activation by Zymosan. 1. Human IgG with specificity for Zymosan enhances alternative pathway activation by Zymosan. J. Immunol. 126:7 (1981) .PubMedGoogle Scholar
  32. 32.
    Smeby, L.C., Jorstad, S.T., Balstad, T., Wideroe, T.E. : Dialyzer generation and plasma clearance of activated complement during hemodialysis. In: Immune and Metabolic Aspects of Therapeutic Blood Purification systems. Smeby, L.C., Jorstad, S.T. and Wideroe, T.E. (eds.) Karger, Basel p. 76 (1986).Google Scholar
  33. 33.
    Weiss, L., Carreno, M.P., Maillet, F.: Antibody dependency of alternative pathway activation during hemodialysis with cuprophane membrane. Complement (abstract) 5:199.Google Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Michel D. Kazatchkine
    • 1
  • Nicole Haeffner-Cavaillon
    • 1
  1. 1.Unité d’Immunopathologie, Inserm U28Hopital BroussaisParisFrance

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