Intercellular adhesion molecule 1 engagement modulates sphingomyelinase and ceramide, supporting uptake of drug carriers by the vascular endothelium.

Arteriosclerosis, Thrombosis, and Vascular Biology
Daniel SerranoSilvia Muro

Abstract

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. We used fluorescence and electron microscopy, inhibitors and knockout tools, cell culture, and mouse models. ICAM-1 engagement by anti-ICAM carriers induced sphingomyelin-enriched engulfment structures. Acid sphingomyelinase (ASM), an acidic enzyme that hydrolyzes sphingomyelin into ceramide (involved in plasmalemma deformability and cytoskeletal reorganization), redistributed to ICAM-1-engagement sites at ceramide-enriched areas. This induced actin stress fibers and carrier endocytosis. Inhibiting ASM impaired ceramide enrichment, engulfment structures, cytoskeletal reorganization, and carrier uptake, which was rescued by supplying this enzyme activity exogenously. Interfering with NHE1 rendered similar outcomes, suggest...Continue Reading

References

Feb 14, 1998·The Journal of Cell Biology·X ZhaF R Maxfield
Jul 8, 2000·Trends in Cell Biology·N W Andrews
Sep 23, 2000·Chemistry and Physics of Lipids·I Tabas
Mar 12, 2002·Traffic·Eunkyung Lee, David A Knecht
Mar 28, 2002·The Journal of Biological Chemistry·Masahiro MurakamiMichael Simons
Mar 18, 2003·Journal of Cell Science·Silvia MuroMichael Koval
Sep 13, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Silvia MuroVladimir R Muzykantov
Oct 18, 2005·Biochimica Et Biophysica Acta·Claudia R BollingerErich Gulbins
Nov 22, 2005·American Journal of Physiology. Lung Cellular and Molecular Physiology·Silvia MuroMichael Koval
Mar 1, 2006·The Journal of Pharmacology and Experimental Therapeutics·Silvia MuroVladimir R Muzykantov
Apr 11, 2006·American Journal of Physiology. Lung Cellular and Molecular Physiology·Radu V Stan
Oct 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lin YangFrancis W Luscinskas
Jul 5, 2007·Nature Reviews. Molecular Cell Biology·Satyajit Mayor, Richard E Pagano
Aug 19, 2007·Cancer Research·Amélie RebillardMarie-Thérèse Dimanche-Boitrel
Aug 25, 2007·Nature Reviews. Immunology·Klaus LeySussan Nourshargh
Dec 29, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Si JinPin-Lan Li
Feb 22, 2008·The Journal of Pharmacology and Experimental Therapeutics·Carmen GarnachoSilvia Muro
Apr 23, 2008·The Journal of Cell Biology·Youssef H ZeidanYusuf A Hannun
Jun 19, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Silvia MuroVladimir R Muzykantov
Aug 2, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Cecilia M DevlinIra Tabas
Nov 22, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Philippe SucoskyAjit P Yoganathan
Apr 23, 2009·Cellular Signalling·Russell W JenkinsYusuf A Hannun
Jun 10, 2010·The Journal of Cell Biology·Christina TamNorma W Andrews
Nov 5, 2010·Journal of Controlled Release : Official Journal of the Controlled Release Society·Andres J CalderonSilvia Muro
Nov 5, 2010·Journal of Controlled Release : Official Journal of the Controlled Release Society·Janet HsuSilvia Muro
Nov 11, 2010·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Rajwinder DhamiEdward H Schuchman

❮ Previous
Next ❯

Citations

Jan 5, 2013·Human Reproduction Update·Xiang XiaoC Yan Cheng
Feb 15, 2017·Experimental Biology and Medicine·Khosrow KhodabandehlouEun Ji Chung
Jul 31, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Rasa GhaffarianSilvia Muro
May 13, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Jingyan HanVladimir R Muzykantov
Jan 13, 2015·Advanced Drug Delivery Reviews·Prarthana V RewatkarMarie-Odile Parat
Apr 23, 2015·PloS One·David Gonzalez-Rodriguez, Abdul I Barakat
Jul 18, 2017·Bioengineering & Translational Medicine·Rachel L Manthe, Silvia Muro
Apr 19, 2012·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Xue-Long JinJie Zhao
May 5, 2016·Wiener medizinische Wochenschrift·Aritz Perez Ruiz de Garibay
Jan 26, 2017·Frontiers in Cell and Developmental Biology·Mary L Kraft
May 19, 2019·Cellular and Molecular Life Sciences : CMLS·Azam SafaryMohammad A Rafi
May 19, 2019·The Journal of Pharmacology and Experimental Therapeutics·Rachel L MantheSilvia Muro
Nov 26, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Melissa A Lopes PinheiroHelga E de Vries
Oct 18, 2018·Frontiers in Physiology·Daniela CesselliAntonio Paolo Beltrami
Jun 25, 2020·Advanced Drug Delivery Reviews·Patrick M GlassmanVladimir R Muzykantov
Jan 22, 2021·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Hanhui ZhongJing Tang
May 12, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Rachel L MantheSilvia Muro
May 16, 2017·Advanced Drug Delivery Reviews·Melani Solomon, Silvia Muro
Nov 23, 2021·Frontiers in Cell and Developmental Biology·Yasuhiko NakaoHarmeet Malhi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.