@article{de35a01f009545068e181dcd07043958,
title = "Ceramide as an endothelial cell surface receptor and a lung-specific lipid vascular target for circulating ligands",
abstract = "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.",
keywords = "Humans, Ligands, COVID-19/metabolism, Ceramides/metabolism, Lung/metabolism, Endothelium, Vascular/metabolism, Receptors, Cell Surface/metabolism, Carrier Proteins/metabolism, Sphingomyelin Phosphodiesterase/metabolism, endothelial cells, acid sphingomyelinase, lung, ceramide, phage display",
author = "Staquicini, {Daniela I} and Marina Card{\'o}-Vila and Rotolo, {Jimmy A} and Staquicini, {Fernanda I} and Tang, {Fenny H F} and Smith, {Tracey L} and Aditya Ganju and Carmine Schiavone and Prashant Dogra and Zhihui Wang and Vittorio Cristini and Giordano, {Ricardo J} and Ozawa, {Michael G} and Driessen, {Wouter H P} and Bettina Proneth and Souza, {Glauco R} and Brinker, {Lina M} and Achraf Noureddine and Snider, {Ashley J} and Daniel Canals and Gelovani, {Juri G} and Irina Petrache and Tuder, {Rubin M} and Obeid, {Lina M} and Hannun, {Yusuf A} and Kolesnick, {Richard N} and Brinker, {C Jeffrey} and Renata Pasqualini and Wadih Arap",
note = "Funding Information: ACKNOWLEDGMENTS. We thank Drs. Webster K. Cavenee and E. Helene Sage for critical reading of the manuscript and Dr.Helen Pickersgill (Life Science Editors) for professional editorial services. P30 Cancer Center Support Grants (CCSG) of the Rutgers Cancer Institute of New Jersey (CA072720 to R.P. and W.A.) and the Memorial Sloan Kettering Institute (CA008748 to R.N.K.); Research awards from the Levy-Longenbaugh Donor-Advised Fund (to R.P. and W.A.); Research awards from the Cockrell Foundation (to P.D. and V.C.); Sponsored Research Agreements from PhageNova Bio and MBrace Therapeutics (all to R.P. and W.A.); and National Cancer Institute (NCI) grant P01 CA097132 (to Y.A.H., L.M.O., and A.J.S.). Publisher Copyright: Copyright {\textcopyright} 2023 the Author(s). Published by PNAS.",
year = "2023",
month = aug,
day = "22",
doi = "10.1073/pnas.2220269120",
language = "English (US)",
volume = "120",
pages = "e2220269120",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "34",
}