Ceramide as an endothelial cell surface receptor and a lung-specific lipid vascular target for circulating ligands

Daniela I. Staquicini, Marina Cardó-Vila, Jimmy A. Rotolo, Fernanda I. Staquicini, Fenny H.F. Tang, Tracey L. Smith, Aditya Ganju, Carmine Schiavone, Prashant Dogra, Zhihui Wang, Vittorio Cristini, Ricardo J. Giordano, Michael G. Ozawa, Wouter H.P. Driessen, Bettina Proneth, Glauco R. Souza, Lina M. Brinker, Achraf Noureddine, Ashley J. Snider, Daniel CanalsJuri G. Gelovani, Irina Petrache, Rubin M. Tuder, Lina M. Obeid, Yusuf A. Hannun, Richard N. Kolesnick, C. Jeffrey Brinker, Renata Pasqualini, Wadih Arap

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


The vascular endothelium from individual organs is functionally specialized, and it displays a unique set of accessible molecular targets. These serve as endothelial cell receptors to affinity ligands. To date, all identified vascular receptors have been proteins. Here, we show that an endothelial lung-homing peptide (CGSPGWVRC) interacts with C16-ceramide, a bioactive sphingolipid that mediates several biological functions. Upon binding to cell surfaces, CGSPGWVRC triggers ceramide-rich platform formation, activates acid sphingomyelinase and ceramide production, without the associated downstream apoptotic signaling. We also show that the lung selectivity of CGSPGWVRC homing peptide is dependent on ceramide production in vivo. Finally, we demonstrate two potential applications for this lipid vascular targeting system: i) as a bioinorganic hydrogel for pulmonary imaging and ii) as a ligand-directed lung immunization tool against COVID-19. Thus, C16-ceramide is a unique example of a lipid-based receptor system in the lung vascular endothelium targeted in vivo by circulating ligands such as CGSPGWVRC.

Original languageEnglish (US)
Article numbere2220269120
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number34
StatePublished - 2023
Externally publishedYes


  • acid sphingomyelinase
  • ceramide
  • endothelial cells
  • lung
  • phage display

ASJC Scopus subject areas

  • General


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