Role of Acid Sphingomyelinase in Icam-1/nhe1-dependent Endocytosis: Implications in Leukocyte Transmigration
نویسندگان
چکیده
Title of Thesis: ROLE OF ACID SPHINGOMYELINASE IN ICAM-1/NHE1-DEPENDENT ENDOCYTOSIS: IMPLICATIONS IN LEUKOCYTE TRANSMIGRATION Daniel Serrano, Master of Science 2010 Thesis directed by: Professor Silvia Muro Fischell Department of Bioengineering, Clark School of Engineering, and Institute for Bioscience and Biotechnology Research Engagement of intercellular adhesion molecule-1 (ICAM-1) on endothelial cells (ECs) by anti-ICAM coated beads generates vesiculization via cell adhesion molecule (CAM)mediated endocytosis, a clathrin-/caveolae-independent pathway involving Na/H exchanger 1 (NHE1). ICAM-1 itself plays a key role in transendothelial migration (TEM) of leukocytes, particularly via the transcellular route. This involves endothelial endocytic vesicles that coalesce into transmigration pores, through which leukocytes transmigrate without disrupting EC junctions. The contribution of CAM-mediated endocytosis to the formation of docking sites and vesicular structures supporting TEM was explored in this study. Results show that the ICAM-1/NHE1-dependent CAM-mediated pathway associates with acid sphingomyelinase and ceramide. This supports plasmalemma deformability and cytoskeleton rearrangement, bridging these events to the formation of endothelial docking structures and vesicles involved in leukocyte transmigration. ROLE OF ACID SPHINGOMYELINASE IN ICAM-1/NHE1-DEPENDENT ENDOCYTOSIS: IMPLICATIONS IN LEUKOCYTE TRANSMIGRATION
منابع مشابه
Intercellular adhesion molecule 1 engagement modulates sphingomyelinase and ceramide, supporting uptake of drug carriers by the vascular endothelium.
OBJECTIVE 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 duri...
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