Interaction of poly(styrene sulfonic acid) with the alternative pathway of the serum complement system.
Bioartificial pancreas, in which the islets of Langerhans 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 preparation of a bioartificial pancreas involves utilizing a membrane including polymeric materials that can inhibit the complement reaction. In this study, we examined the effects of poly(styrene sulfonic acid) (PSSa) on the alternative pathway of the serum complement system to identify the mechanism(s) involved. PSSa was dissolved in pooled normal human serum (NHS), and the mixtures were incubated at 37 degrees C for 30 min. Complement activities in sera were determined by hemolytic assays. Amounts of complement activation products released were determined by ELISA. Interactions of PSSa with complement components and fragments were examined with electrophoresis and immunoblotting. From these examinations, it appeared that the manner of PSSa effects on the alternative pathway (AP) highly depends on its concentration. PSSa seemingly acted as an activator when its concentration was 0.005 g/dl to 0.05 g/dl, while it acted as an inhibitor when its concentration was more than 0.1 g/dl. In terms of activation or inhibition of the AP, forming complex of PSSa with factor H induced activation, and that with factor D induced inhibition.
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
D001672:Biocompatible Materials / Q000737:chemistry*; D003167:Complement Activation; D003176:Complement C3 / Q000737:chemistry; D011416:Complement Factor D / Q000737:chemistry; D017242:Complement Factor H / Q000737:chemistry; D003165:Complement System Proteins; D003920:Diabetes Mellitus / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000737:chemistry; D004587:Electrophoresis, Agar Gel; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006461:Hemolysis; D006801:Humans; D015151:Immunoblotting; D007328:Insulin / Q000378:metabolism; D007525:Isoelectric Focusing; D008954:Models, Biological; D019397:Pancreas, Artificial; D000071228:Polyelectrolytes; D011108:Polymers / Q000737:chemistry; D011137:Polystyrenes / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D013451:Sulfonic Acids / Q000737:chemistry; D013696:Temperature; D013997:Time Factors
D001672:Biocompatible Materials; D003176:Complement C3; D011416:Complement Factor D; D017242:Complement Factor H; D003165:Complement System Proteins; D004492:Edetic Acid; D007328:Insulin; D000071228:Polyelectrolytes; D011108:Polymers; D011137:Polystyrenes; D013451:Sulfonic Acids; C493495:CFH protein, human; C003321:polystyrene sulfonic acid; C493488:CFD protein, human