TY - JOUR
T1 - Ceramide as an endothelial cell surface receptor and a lung-specific lipid vascular target for circulating ligands
AU - Staquicini, Daniela I.
AU - Cardó-Vila, Marina
AU - Rotolo, Jimmy A.
AU - Staquicini, Fernanda I.
AU - Tang, Fenny H.F.
AU - Smith, Tracey L.
AU - Ganju, Aditya
AU - Schiavone, Carmine
AU - Dogra, Prashant
AU - Wang, Zhihui
AU - Cristini, Vittorio
AU - Giordano, Ricardo J.
AU - Ozawa, Michael G.
AU - Driessen, Wouter H.P.
AU - Proneth, Bettina
AU - Souza, Glauco R.
AU - Brinker, Lina M.
AU - Noureddine, Achraf
AU - Snider, Ashley J.
AU - Canals, Daniel
AU - Gelovani, Juri G.
AU - Petrache, Irina
AU - Tuder, Rubin M.
AU - Obeid, Lina M.
AU - Hannun, Yusuf A.
AU - Kolesnick, Richard N.
AU - Brinker, C. Jeffrey
AU - Pasqualini, Renata
AU - Arap, Wadih
N1 - Publisher Copyright:
Copyright © 2023 the Author(s). Published by PNAS.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - acid sphingomyelinase
KW - ceramide
KW - endothelial cells
KW - lung
KW - phage display
UR - https://www.scopus.com/pages/publications/85168209845
U2 - 10.1073/pnas.2220269120
DO - 10.1073/pnas.2220269120
M3 - Article
C2 - 37579172
AN - SCOPUS:85168209845
SN - 0027-8424
VL - 120
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 34
M1 - e2220269120
ER -