Dextran sulfate as a material for the preparation of a membrane for immunoisolation.
Bioartificial pancreas, in which the islets of Langerhans (islets) are enclosed in an 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. In our series of studies, we have examined interactions of various polyanions with the complement system to search for potential complement inhibitors. In this study, we concentrated our efforts to clarify the effects of dextran sulfate on the complement system. All of the dextran sulfates examined inhibited the complement activation through both classical and alternative pathways as previously reported. In addition to their inhibitory effects, a certain species of dextran sulfate (molecular mass 10 kDa, degree of sulfonation in a pyranose ring 1.99) specifically degraded C3 without complement activation and, thus, anaphylatoxins that trigger inflammatory reactions were not generated. These facts suggest that a membrane including dextran sulfate effectively protects the islet cells from humoral immunity in addition to not triggering inflammatory reactions. These properties of the membrane make it suitable for a bioratificial pancreas.
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
D021522:Bioartificial Organs; D003176:Complement C3 / Q000276:immunology*; D003181:Complement C4 / Q000276:immunology / Q000378:metabolism; D015935:Complement C4b; D003182:Complement C5 / Q000276:immunology; D016264:Dextran Sulfate / Q000737:chemistry* / Q000276:immunology*; D006801:Humans; D008567:Membranes, Artificial; D010179:Pancreas / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D044967:Serum / Q000737:chemistry / Q000276:immunology
D003176:Complement C3; D003181:Complement C4; D003182:Complement C5; D008567:Membranes, Artificial; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d; D016264:Dextran Sulfate