A study of the xenoantigenicity of adult pig islets cells

被引:64
作者
Komoda, H
Miyagawa, S
Kubo, T
Kitano, E
Kitamura, H
Omori, T
Ito, T
Matsuda, H
Shirakura, R
机构
[1] Osaka Univ, Grad Sch Med, Dept Regenerat Med, Div Organ Transplantat, Suita, Osaka 5650871, Japan
[2] Osaka Univ, Grad Sch Med, Dept Regenerat Med, Div Surg, Suita, Osaka 5650871, Japan
[3] Anim Engn Res Inst, Tsukuba, Ibaraki, Japan
[4] Osaka Prefecture Coll Hlth Sci, Dept Clin Lab Sci, Osaka, Japan
关键词
complement; Hanganutziu-Deicher antigen; N-linked sugar; non-alpha Gal antigen; pig islets;
D O I
10.1111/j.1399-3089.2004.00121.x
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background: The pig pancreas is considered to be the most suitable source of islets for xenotransplantation into patients with type I diabetes. The purpose of this study was to assess the antigenicity of pig islets, including the Galalpha1-3Galbeta1-4GlcNAc-R (the alpha-Gal) and Hanganutziu-Deicher (H-D) antigens, and the pathway involved in human complement activation. Methods: The expression of alpha-Gal on islets from adult pigs was investigated by immunohistochemical staining and flowcytometric analysis. The alpha1,3 galactosyltransferase (alpha1,3GT) activity of islets was determined by high-performance liquid chromatography. Antigenicity to human natural antibodies, including the H-D antigen of pig islets was next examined by treatment of pig islets with tunicamycin, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) and/or neuraminidase. In addition, complement-mediated islets lysis was examined using factor D-deficient and C1-deficient sera. Results: Adult pig islets expressed negligible amounts of alpha-Gal epitope, and alpha1,3GT activity was also undetectable. However, human natural antibodies, immunoglobulin G and M, and the anti H-D antibody react to the adult islet. Treatment of pig islets with tunicamycin, but not PDMP, led to a drastic reduction in antigenicity to human serum, indicating the importance of N-linked sugars on the islets. Neuraminidase treatment indicated the presence of, not only the H-D antigen, but also other sialic acid antigens that reacted with the human natural antibody. The complement deposition of C4, C3 and factor B on islets was demonstrated. The alternative pathway-mediated pig islet killing accounted for approximately 30% of that by the total complement pathway. Conclusion: The origin of antigenicity of pig islets is mainly N-linked sugars including sialic acid antigens, but not the alpha-Gal, and pig islets can be injured by both the classical and the alternative complement pathway in human serum.
引用
收藏
页码:237 / 246
页数:10
相关论文
共 32 条
[1]  
ASAOKA H, 1992, IMMUNOL LETT, V32, P91
[2]  
Bennet W, 2000, TRANSPLANTATION, V69, P711
[3]   Clinical xenotransplantion - how close are we? [J].
Cooper, DKC .
LANCET, 2003, 362 (9383) :557-559
[4]   OLIGOSACCHARIDES AND DISCORDANT XENOTRANSPLANTATION [J].
COOPER, DKC ;
KOREN, E ;
ORIOL, R .
IMMUNOLOGICAL REVIEWS, 1994, 141 :31-58
[5]   Evolution of the lectin-complement pathway and its role in innate immunity [J].
Fujita, T .
NATURE REVIEWS IMMUNOLOGY, 2002, 2 (05) :346-353
[6]   Effect of hybrid complement regulatory proteins on xenogeneic cells [J].
Fukuta, D ;
Miyagawa, S ;
Kubo, T ;
Matsunami, K ;
Shirasu, A ;
Hattori, H ;
Shirakura, R .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2003, 306 (02) :476-482
[7]   A sensitive assay for measuring α-gal epitope expression on cells by a monoclonal anti-Gal antibody [J].
Galili, U ;
LaTemple, DC ;
Radic, MZ .
TRANSPLANTATION, 1998, 65 (08) :1129-1132
[8]   TRANSPLANTATION OF PORCINE FETAL PANCREAS TO DIABETIC-PATIENTS [J].
GROTH, CG ;
KORSGREN, O ;
TIBELL, A ;
TOLLEMAR, J ;
MOLLER, E ;
BOLINDER, J ;
OSTMAN, J ;
REINHOLT, FP ;
HELLERSTROM, C ;
ANDERSSON, A .
LANCET, 1994, 344 (8934) :1402-1404
[9]   The molecular basis for the absence of N-glycolylneuraminic acid in humans [J].
Irie, A ;
Koyama, S ;
Kozutsumi, Y ;
Kawasaki, T ;
Suzuki, A .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (25) :15866-15871
[10]   Lack of antibody production against Hanganutziu-Deicher (H-D) antigens with N-glycolylneuraminic acid in patients with porcine exposure history [J].
Kobayashi, T ;
Yokoyama, I ;
Suzuki, A ;
Abe, M ;
Hayashi, S ;
Matsuda, H ;
Morozumi, K ;
Breimer, ME ;
Rydberg, L ;
Groth, CG ;
Tibell, A ;
Korsgren, O ;
Takagi, H ;
Nakao, A .
XENOTRANSPLANTATION, 2000, 7 (03) :177-180