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Engagement of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells by ICAM-1-targeted carriers induces cell adhesion molecule-mediated endocytosis, providing intraendothelial delivery of therapeutics. This pathway differs from classical endocytic mechanisms and invokes aspects of endothelial signaling during inflammation. ICAM-1 interacts with Na(+)/H(+) exchanger NHE1 during endocytosis, but it is unclear how this regulates plasmalemma and cytoskeletal changes. We studied such aspects in this work.

Intercellular Adhesion Molecule 1 Engagement Modulates Sphingomyelinase and Ceramide, Supporting Uptake of Drug Carriers by the Vascular Endothelium