Open AccessThe importance of sialic acid, pH and ion concentration on the interaction of uromodulin and complement factor H
Author(s) -
Bai Lufeng,
Xie Qiuyu,
Xia Min,
Gong Kunjing,
Wang Na,
Chen Yuqing,
Zhao Minghui
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16492
Subject(s) - tamm–horsfall protein , sialic acid , chemistry , complement system , alternative complement pathway , lectin , biochemistry , factor h , glycoprotein , immunology , biology , immune system , urine
Abstract Uromodulin (UMOD) can bind complement factor H (cFH) and inhibit the activation of complement alternative pathway (AP) by enhancing the cofactor activity of cFH on degeneration of C3b. UMOD, an N‐glycans‐rich glycoprotein, is expressed in thick ascending limb of Henle's loop where the epithelia need to adapt to gradient change of pH and ion concentration. ELISA‐based cofactor activity of cFH and erythrocytes haemolytic assay was used to measure the impact of native and de‐glycosylated UMOD on the functions of cFH. The binding assay was performed under different pH and ion concentrations, using ELISA. The levels of sialic acid on UMOD, from healthy controls and patients with chronic kidney disease (CKD), were also detected by lectin‐ELISA. It was shown that removal of glycans decreased the binding between UMOD and cFH and abolished the ability of enhancing C3b degradation. In acidic condition, the binding became stronger, but it reduced as sodium concentration increased. A significant decrease of α‐2,3 sialic acids on UMOD was observed in CKD patients compared with that of healthy individuals. The sialic acids on UMOD, local pH and sodium concentration could impact the binding capacity between UMOD and cFH and thus regulate the activation of complement AP.