Interaction of poly(styrene sulfonic acid) with the classical pathway of the serum complement system.
Bioartificial pancreas, in which the islets of Langerhans (islets) are enclosed in artificial membrane to be protected from the host immune system, is expected to be a promising medical device to treat patients who suffer from insulin-dependent diabetes. Our strategy for the preparation of a bioartificial pancreas involves utilizing a membrane including polymeric materials that can inhibit the complement. When we examined a membrane containing poly(styrene sulfonic acid), long survival of islets enclosed in the membrane was observed in recipients carrying antibodies against islet cells. This fact stimulated us to start examinations of effects of PSSa on the complement system. In this study, we examined effects of PSSa on the classical pathway (CP) of the serum complement system to identify the mechanism(s) involved. The electric static interaction between cationic C1q (pI 9.3) and anionic PSSa induces PSSa-C1q complex formation. The dissociation of C1q(r2s2) complex by PSSa results inactivation of the CP activity. Those results indicate that PSSa was not an activator of the CP, but an inhibitor of CP activation. This study clarifies the mechanism by which PSSa protects islets in a microcapsule from the humoral immunity of the recipient carrying anti-islet antibodies. A microcapsule containing PSSa seems to effectively protect the islet from attacks of the host immune system after transplantation carrying antibodies against islet cells.
Murakami
Yoshinobu
Y
Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Iwata
Hiroo
H
Kitano
Etsuko
E
Kitamura
Hajime
H
Ikada
Yoshito
Y
D000818:Animals; D001323:Autoantibodies / Q000187:drug effects; D015551:Autoimmunity / Q000187:drug effects; D021522:Bioartificial Organs; D001672:Biocompatible Materials / Q000494:pharmacology; D001769:Blood / Q000276:immunology; D003167:Complement Activation / Q000187:drug effects*; D015922:Complement C1q / Q000378:metabolism; D003169:Complement Inactivator Proteins / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology*; D008567:Membranes, Artificial; D019397:Pancreas, Artificial; D011137:Polystyrenes / Q000378:metabolism / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D011485:Protein Binding
D001323:Autoantibodies; D001672:Biocompatible Materials; D003169:Complement Inactivator Proteins; D008567:Membranes, Artificial; D011137:Polystyrenes; D020011:Protective Agents; C003321:polystyrene sulfonic acid; D015922:Complement C1q