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Titolo:
ALPHA-GALACTOSYL OLIGOSACCHARIDES CONJUGATED WITH POLYETHYLENE-GLYCOLAS POTENTIAL INHIBITORS OF HYPERACUTE REJECTION UPON XENOTRANSPLANTATION
Autore:
NAGASAKA T; KOBAYASHI T; MURAMATSU H; FUJIMOTO H; MATSUO I; AJISAKA K; KADOMATSU K; HAYASHI S; YOKOYAMA I; HAYAKAWA A; MURAMATSU T; TAKAGI H;
Indirizzi:
NAGOYA UNIV,SCH MED,DEPT SURG 2 NAGOYA AICHI 466 JAPAN NAGOYA UNIV,SCH MED,DEPT SURG 2 NAGOYA AICHI 466 JAPAN NAGOYA UNIV,SCH MED,DEPT BIOCHEM 1 NAGOYA AICHI 466 JAPAN NAGOYA UNIV,SCH MED,EQUIPMENT CTR RES & EDUC NAGOYA AICHI 466 JAPAN MEIJI MILK PROD CO LTD,MEIJI INST HLTH SCI ODAWARA 540 JAPAN
Titolo Testata:
Biochemical and biophysical research communications
fascicolo: 3, volume: 232, anno: 1997,
pagine: 731 - 736
SICI:
0006-291X(1997)232:3<731:AOCWP>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
MONOMETHOXYPOLYETHYLENE GLYCOL; ANTIBODIES; CELLS; TRANSPLANTATION; INDUCTION; TOLERANCE; ASSAY; LIFE; MICE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
27
Recensione:
Indirizzi per estratti:
Citazione:
T. Nagasaka et al., "ALPHA-GALACTOSYL OLIGOSACCHARIDES CONJUGATED WITH POLYETHYLENE-GLYCOLAS POTENTIAL INHIBITORS OF HYPERACUTE REJECTION UPON XENOTRANSPLANTATION", Biochemical and biophysical research communications, 232(3), 1997, pp. 731-736

Abstract

Antibodies to an alpha-galactosyl saccharide structure are mainly responsible for hyperacute rejection after pig-to-primate xenotransplantation. The beneficial effect of alpha-galactosyl oligosaccharides has been shown on the inhibition of anti-pig natural antibodies. We synthesized polyethylene glycol (PEG)conjugates of alpha-galactosyl disaccharide (Pi) and trisaccharide (Tri) as potential inhibitors of the rejection reaction. The half lives of Di, Tri, PEG-conjugated Pi (Pi-PEG) and PEG-conjugated Tri (Tri-PEG) were 18.1 +/- 2.3 min, 20.2 +/- 0.9 min, 38.7 +/- 2.8 min and 35.8 +/- 1.6 min, respectively. Furthermore, Pi-PEG and Tri-PEG showed biphasic clearance, and their half lives at the second phase were longer than 10 hours. PEG-conjugated oligosaccharides (Pi-PEG, Tri-PEG) markedly inhibited cytotoxic action of human sera to pig kidney cell line (PK15) compared to unconjugated oligosaccharides (Pi, Tri). The binding of IgM antibodies to PK15 cells, however, was more strongly blocked by unconjugated oligosaccharides than PEG-conjugated oligosaccharides. This phenomenon can be explained by the finding that PEG has anti-complement activity and masks antigenic sites of oligosaccharides. In conclusion, conjugation of PEG to oligosaccharides provided two beneficial effects; prolonged intravascular retentiontime and anti-complement activity, upon systemic application of the oligosaccharides. The present findings opened a new approach to treatment of hyperacute rejection after xenotransplantation. (C) 1997 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/09/20 alle ore 12:08:39