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

oleh: Ségolène Ladaigue, Anne-Charlotte Lefranc, Khadidiatou Balde, Monica Quitoco, Emilie Bacquer, Didier Busso, Guillaume Piton, Jordane Dépagne, Nathalie Déchamps, Nao Yamakawa, Louise Debusschere, Chunxue Han, Fabrice Allain, Valérie Buard, Georges Tarlet, Agnès François, Vincent Paget, Fabien Milliat, Olivier Guipaud

Format: Article
Diterbitkan: Elsevier 2022-12-01

Deskripsi

Summary: 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.