iScience (Dec 2022)

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

  • 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

Journal volume & issue
Vol. 25, no. 12
p. 105482

Abstract

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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.

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