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

Overview

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.

authors

publication date

  • August 14, 2023

Research

keywords

  • COVID-19

Identity

PubMed Central ID

  • PMC10450669

Scopus Document Identifier

  • 85168209845

Digital Object Identifier (DOI)

  • 10.1073/pnas.2220269120

PubMed ID

  • 37579172

Additional Document Info

volume

  • 120

issue

  • 34