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Resistance of neonatal porcine Sertoli cells to human xenoantibody and complement‐mediated lysis is associated with low expression of α‐Gal and high production of clusterin and CD59
Author(s) -
Yin Zhuzeng,
Wang Lu,
Xiang Ying,
Ruan Yongle,
Li Junhua,
Wang Ximo,
Ichim Thomas E.,
Chen Shi,
Chen Gang
Publication year - 2010
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/j.1399-3089.2010.00581.x
Subject(s) - clusterin , cd59 , lysis , microbiology and biotechnology , complement (music) , biology , chemistry , andrology , immunology , complement system , medicine , apoptosis , immune system , biochemistry , gene , complementation , phenotype
Yin Z, Wang L, Xiang Y, Ruan Y, Li J, Wang X, Ichim TE, Chen S, Chen G. Resistance of neonatal porcine Sertoli cells to human xenoantibody and complement‐mediated lysis is associated with low expression of α‐Gal and high production of clusterin and CD59. Xenotransplantation 2010; 17: 215–223. © 2010 John Wiley & Sons A/S. Abstract: Background: Porcine Sertoli cells have an inherent resistance to human xenoreactive antibody and complement‐mediated lysis, however, the mechanisms of protection are still unclear. Methods: Neonatal porcine Sertoli cells (NPSCs) were isolated from testes of 10 to 15‐day‐old piglets. Immortalized porcine aortic endothelial cells (iPECs) were used as control cells. An in vitro humoral injury model was used to assess whether NPSCs could resist human xenoantibody and complement‐mediated lysis. Expressions of α‐Gal, clusterin, CD59, CD46, and CD55 were examined to investigate the possible mechanisms of the immunoprotection of NPSCs. Results: Compared with iPECs, NPSCs significantly resisted human natural antibody and complement‐mediated lysis when incubated with 20% normal human serum (NHS) in vitro (24.38 ± 0.50 vs. 53.13 ± 14.53%, P < 0.01). Mechanistically, NPSCs expressed lower level of α‐Gal (Gmean: 41.78 ± 2.39 vs. 95.17 ± 2.39, P < 0.01), which was correlated with decreased binding of human xenoreactive IgG and IgM. Additionally, NPSCs expressed higher level of clusterin measured by both Western blot and fluorescence‐activated cell sorter analysis and expressed more CD59 mRNA detected by reverse‐transcription polymerase chain reaction. Conclusions: These data demonstrate that the resistance of NPSCs to human xenoantibody and complement‐mediated lysis is associated with low expression of xenoantigen α‐Gal and high production of the complement inhibitors clusterin and CD59.