Human ST3Gal II and ST6GalNAc IV genes increase human serum‐mediated cytotoxicity to xenogeneic cells

Author:

Choi Hyunju1,Song Kwon‐Ho12,Kim Hee‐Do1,Park Jun‐Young1,Lee Young‐Choon3,Choi Hee‐Jung4ORCID,Kim Cheorl‐Ho1ORCID

Affiliation:

1. Molecular and Cellular Glycobiology Unit Department of Biological Sciences SungKyunKwan University Suwon South Korea

2. Department of Cell Biology Daegu Catholic University School of Medicine Daegu South Korea

3. Department of Medicinal Biotechnology College of Health Sciences Dong‐A University Saha‐Gu Busan South Korea

4. Jin BioCell Co., Ltd. R&D Center, #101‐103 National Clinical Research Center for Korean Medicine Pusan National University Korean Medicine Hospital Yangsan Gyeongsangnam‐do Republic of Korea

Abstract

AbstractCarbohydrate‐antigens widely existed on glycoproteins and glycosphingolipids of all mammalian cells play a crucial role in self‐defense and immunity. Xeno‐reactive antibodies included in natural human sera play a protecting role in an acute phase‐rejection of xenotransplantation. In this study, we investigated the effect of an alteration of glycosylation‐pattern, caused by human sialyltransferases such as hST3Gal II or hST6GalNAc IV, on human serum mediated cytotoxicity in pig kidney PK15 cells. From LDH cytotoxicity assay, cytotoxicity to human serum was significantly increased in hST3Gal II and hST6GalNAc IV‐transfected PK15 cells, as compared to the control. In the hST6Gal I‐carrying cells, the cytotoxicity to human serum was rather decreased. Moreover, flow cytometry analysis revealed that an alteration of pig glycosylation‐pattern by hST3Gal II or hST6GalNAc IV influences on a binding of human IgM or IgG, respectively, in pig kidney cells, regardless of Gal antigen alteration. Finally, we found that hST6GalNAc IV contributed to increase of terminal disialylated tetrasaccharide structure, disialyl T antigen, as evidenced by increase of the MAL II lectin binding capacity in the hST6GalNAc IV‐transfected PK15 cells, compared with control. Therefore, our results suggest that carbohydrate antigens, such as disialyl T antigen, newly synthesized by the ST3Gal II‐ and ST6GalNAc IV are potentially believed to be new xeno‐reactive elements.

Publisher

Wiley

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