Reduction in disialyl-T antigen levels in mice deficient for both St6galnac3 and St6galnac4 results in blood filling of lymph nodes

• Published in: Scientific reports 2023-06, Vol.13 (1), p.10582-10582, Article 10582
• Main Authors: Fuseya, Sayaka, Izumi, Hiroyuki, Hamano, Ayane, Murakami, Yuka, Suzuki, Riku, Koiwai, Rikako, Hayashi, Takuto, Kuno, Atsushi, Takahashi, Satoru, Kudo, Takashi
• Format: Article
• Language: English
• Subjects: 631/337/458/1524; 631/45/221; Animals; Antigens, Viral, Tumor - analysis; Antigens, Viral, Tumor - metabolism; Cadherins; Cell Membrane; Cell surface; Glycolipids; Glycoproteins; Hemorrhage; Hemorrhage - genetics; Hemorrhage - metabolism; Humanities and Social Sciences; Lymph nodes; Lymph Nodes - blood supply; Lymphatic system; Mice; Mice, Knockout; multidisciplinary; Science; Science (multidisciplinary); Sialyltransferases - genetics; Sialyltransferases - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-37363-y

Sialic acid (SA) is present at the terminal ends of carbohydrate chains in glycoproteins and glycolipids and is involved in various biological phenomena. The biological function of the disialyl-T (SAα2-3Galβ1-3(SAα2-6)GalNAcα1- O -Ser/Thr) structure is largely unknown. To elucidate the role of disialyl-T structure and determine the key enzyme from the N -acetylgalactosaminide α2,6-sialyltransferase (St6galnac) family involved in its in vivo synthesis, we generated St6galnac3 - and St6galnac4 -deficient mice. Both single-knockout mice developed normally without any prominent phenotypic abnormalities. However, the St6galnac3 :: St6galnact4 double knockout (DKO) mice showed spontaneous hemorrhage of the lymph nodes (LN). To identify the cause of bleeding in the LN, we examined podoplanin, which modifies the disialyl-T structures. The protein expression of podoplanin in the LN of DKO mice was similar to that in wild-type mice. However, the reactivity of MALII lectin, which recognizes disialyl-T, in podoplanin immunoprecipitated from DKO LN was completely abolished. Moreover, the expression of vascular endothelial cadherin was reduced on the cell surface of high endothelial venule (HEV) in the LN, suggesting that hemorrhage was caused by the structural disruption of HEV. These results suggest that podoplanin possesses disialyl-T structure in mice LN and that both St6galnac3 and St6galnac4 are required for disialyl-T synthesis.