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Staquicini, D.I.* ; Cardó-Vila, M.* ; Rotolo, J.A.* ; Staquicini, F.I.* ; Tang, F.H.F.* ; Smith, T.L.* ; Ganju, A.* ; Schiavone, C.* ; Dogra, P.* ; Wang, Z.* ; Cristini, V.* ; Giordano, R.J.* ; Ozawa, M.G.* ; Driessen, W.* ; Proneth, B. ; Souza, G.R.* ; Brinker, L.M.* ; Noureddine, A.* ; Snider, A.J.* ; Canals, D.* ; Gelovani, J.G.* ; Petrache, I.* ; Tuder, R.M.* ; Obeid, L.M.* ; Hannun, Y.A.* ; Kolesnick, R.N.* ; Brinker, C.J.* ; Pasqualini, R.* ; Arap, W.*

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

Proc. Natl. Acad. Sci. U.S.A. 120:e2220269120 (2023)

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Acid Sphingomyelinase ; Ceramide ; Endothelial Cells ; Lung ; Phage Display; Apoptosis; Sphingomyelinase; Heterogeneity; Cancer; Alpha; Sphingolipids; Metabolism; Selection; Peptides; Drug

ISSN (print) / ISBN 0027-8424

e-ISSN 1091-6490

Journal Proceedings of the National Academy of Sciences of the United States of America

Quellenangaben Volume: 120, Issue: 34, Article Number: e2220269120

Publisher National Academy of Sciences

Publishing Place 2101 Constitution Ave Nw, Washington, Dc 20418 Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Metabolism and Cell Death (MCD)

Grants PhageNova Bio and MBrace Therapeutics
National Cancer Institute (NCI)
Cockrell Foundation
Levy-Longenbaugh Donor-Advised Fund
Memorial Sloan Kettering Institute
P30 Cancer Center Support Grants (CCSG) of the Rutgers Cancer Institute of New Jersey