A role for endothelial alpha-mannosidase MAN1C1 in radiation-induced immune cell recruitment

• Published in: iScience 2022-12, Vol.25 (12), p.105482-105482, Article 105482
• Main Authors: Ladaigue, Ségolène, Lefranc, Anne-Charlotte, Balde, Khadidiatou, Quitoco, Monica, Bacquer, Emilie, Busso, Didier, Piton, Guillaume, Dépagne, Jordane, Déchamps, Nathalie, Yamakawa, Nao, Debusschere, Louise, Han, Chunxue, Allain, Fabrice, Buard, Valérie, Tarlet, Georges, François, Agnès, Paget, Vincent, Milliat, Fabien, Guipaud, Olivier
• Format: Article
• Language: English
• Subjects: Biochemistry; Cell biology; Functional aspects of cell biology; Immunology; Life Sciences
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.105482

Radiation therapy damages tumors and normal tissues, probably in part through the recruitment of immune cells. Endothelial high-mannose N-glycans are, in particular, involved in monocyte-endothelium interactions. Trimmed by the class I α-mannosidases, these structures are quite rare in normal conditions. Here, we show that the expression of the endothelial α-mannosidase MAN1C1 protein decreases after irradiation. We modeled two crucial steps in monocyte recruitment by developing in vitro real-time imaging models. Inhibition of MAN1C1 expression by siRNA gene silencing increases the abundance of high-mannose N-glycans, improves the adhesion of monocytes on endothelial cells in flow conditions and, in contrast, decreases radiation-induced transendothelial migration of monocytes. Consistently, overexpression of MAN1C1 in endothelial cells using lentiviral vectors decreases the abundance of high-mannose N-glycans and monocyte adhesion and enhances transendothelial migration of monocytes. Hence, we propose a role for endothelial MAN1C1 in the recruitment of monocytes, particularly in the adhesion step to the endothelium. [Display omitted] •Irradiation of endothelial cells (ECs) boosts monocyte adhesion and transmigration•Irradiation of ECs decreases the expression of class I alpha-mannosidase 1 (MAN1C1)•MAN1C1 regulates high-mannose N-glycan abundance in ECs•MAN1C1 contributes to radiation-induced interactions between ECs and monocytes Biochemistry; Immunology; Cell biology; Functional aspects of cell biology