Intercellular Adhesion Molecule-1 (ICAM-1) Regulates Endothelial Cell Motility through a Nitric Oxide-dependent Pathway*

Coordinated regulation of endothelial cell migration is an integral process during angiogenesis. However, molecular mechanisms regulating endothelial cell migration remain largely unknown. Increased expression of cell adhesion molecules has been implicated during angiogenesis, yet the precise role of these molecules is unclear. Here, we examined the hypothesis that intercellular adhesion molecule-1 (ICAM-1) is important for endothelial cell migration. Total cell displacement and directional migration were significantly attenuated in ICAM-1-deficient endothelium. Closer examination of ICAM-1-deficient cells revealed decreased Akt Thr308 and endothelial nitric-oxide synthase Ser1177 phosphorylation and NO bioavailability, increased actin stress fiber formation, and a lack of distinct cell polarity compared with wild-type endothelium. Supplementation of ICAM-1 mutant cells with the NO donor DETA NONOate (0.1 μm) corrected the migration defect, diminished stress fiber formation, and enhanced pseudopod and uropod formation. These data demonstrate that ICAM-1 facilitates the development of cell polarity and modulates endothelial cell migration through a pathway regulating endothelial nitric-oxide synthase activation and organization of the actin cytoskeleton.

[1]  D. Cheresh,et al.  The role of alphav integrins during angiogenesis: insights into potential mechanisms of action and clinical development. , 1999, The Journal of clinical investigation.

[2]  D. Bullard,et al.  In vitro culture and characterization of gene targeted mouse endothelium. , 2001, Acta physiologica Scandinavica.

[3]  R. D. Rudic,et al.  Functional Reconstitution of Endothelial Nitric Oxide Synthase Reveals the Importance of Serine 1179 in Endothelium-Dependent Vasomotion , 2002, Circulation research.

[4]  C M Doerschuk,et al.  The p38 Mitogen-Activated Protein Kinase Mediates Cytoskeletal Remodeling in Pulmonary Microvascular Endothelial Cells Upon Intracellular Adhesion Molecule-1 Ligation1 , 2001, The Journal of Immunology.

[5]  G. Camussi,et al.  Nitric oxide mediates angiogenesis induced in vivo by platelet-activating factor and tumor necrosis factor-alpha. , 1997, The American journal of pathology.

[6]  D. Staunton,et al.  Association of intercellular adhesion molecule-1 (ICAM-1) with actin- containing cytoskeleton and alpha-actinin , 1992, The Journal of cell biology.

[7]  Sean P. Palecek,et al.  Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness , 1997, Nature.

[8]  A. Orr,et al.  Thrombospondin signaling through the calreticulin/LDL receptor-related protein co-complex stimulates random and directed cell migration , 2003, Journal of Cell Science.

[9]  M. Goligorsky,et al.  Nitric oxide modulation of focal adhesions in endothelial cells. , 1999, American journal of physiology. Cell physiology.

[10]  M. Terashima,et al.  Nitric oxide regulates actin reorganization through cGMP and Ca2+/calmodulin in RAW 264.7 cells , 2001 .

[11]  D A Lauffenburger,et al.  Mathematical model for the effects of adhesion and mechanics on cell migration speed. , 1991, Biophysical journal.

[12]  B. Han,et al.  CCK independently activates intracellular trypsinogen and NF-kappaB in rat pancreatic acinar cells. , 2001, American journal of physiology. Cell physiology.

[13]  R. Macallister,et al.  Autoregulation of nitric oxide‐soluble guanylate cyclase‐cyclic GMP signalling in mouse thoracic aorta , 1999, British journal of pharmacology.

[14]  D. Bullard,et al.  Essential role of ICAM-1 in mediating monocyte adhesion to aortic endothelial cells. , 2001, American journal of physiology. Cell physiology.

[15]  Y. Kiuchi,et al.  A novel effect of polymorphonuclear leukocytes in the facilitation of angiogenesis. , 2000, Life sciences.

[16]  Hyung Jin Kim,et al.  Vascular Endothelial Growth Factor Expression of Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule 1 (VCAM-1), and E-selectin through Nuclear Factor-κB Activation in Endothelial Cells* , 2001, The Journal of Biological Chemistry.

[17]  J. Bischoff,et al.  Noninflammatory expression of E-selectin is regulated by cell growth. , 1999, Blood.

[18]  G. Dunn.  The locomotory machinery of fibroblasts. , 1980, European journal of cancer.

[19]  Ivar Giaever,et al.  Podokinesis in endothelial cell migration: role of nitric oxide. , 1998, American journal of physiology. Cell physiology.

[20]  M. Labow,et al.  Defective development of the embryonic and extraembryonic circulatory systems in vascular cell adhesion molecule (VCAM-1) deficient mice. , 1995, Development.

[21]  Donna J. Webb,et al.  Adhesion assembly, disassembly and turnover in migrating cells – over and over and over again , 2002, Nature Cell Biology.

[22]  J. Isner,et al.  Role of endothelial nitric oxide synthase in endothelial cell migration. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[23]  A. Ridley.  Rho GTPases and cell migration. , 2001, Journal of cell science.

[24]  A. Koch,et al.  Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1 , 1995, Nature.

[25]  G. Prestwich,et al.  Phosphatidylinositol (3,4,5)P3 Is Essential but Not Sufficient for Protein Kinase B (PKB) Activation; Phosphatidylinositol (3,4)P2 Is Required for PKB Phosphorylation at Ser-473 , 2002, The Journal of Biological Chemistry.

[26]  A. Vaheri,et al.  Association of Ezrin with Intercellular Adhesion Molecule-1 and -2 (ICAM-1 and ICAM-2) , 1998, The Journal of Biological Chemistry.

[27]  P. Weissberg,et al.  Expression of angiogenic factor thymidine phosphorylase and angiogenesis in human atherosclerosis , 2000, The Journal of pathology.

[28]  Marina Ziche,et al.  Nitric Oxide and Angiogenesis , 2000, Journal of Neuro-Oncology.

[29]  J. Woodgett,et al.  Unravelling the activation mechanisms of protein kinase B/Akt , 2003, FEBS letters.

[30]  C. Kevil.  Endothelial cell activation in inflammation: lessons from mutant mouse models. , 2003, Pathophysiology : the official journal of the International Society for Pathophysiology.

[31]  H. Kleinman,et al.  Angiogenic activity of human soluble intercellular adhesion molecule-1. , 1999, Cancer research.

[32]  R. Busse,et al.  Increased nitrovasodilator sensitivity in endothelial nitric oxide synthase knockout mice: role of soluble guanylyl cyclase. , 2000, Hypertension.

[33]  Yunchao Su,et al.  Regulation of endothelial nitric oxide synthase by the actin cytoskeleton. , 2003, American journal of physiology. Cell physiology.

[34]  P. Cohen,et al.  Mechanism of activation of protein kinase B by insulin and IGF‐1. , 1996, The EMBO journal.

[35]  G. Garcı́a-Cardeña,et al.  Nitric oxide synthase inhibitors attenuate transforming-growth-factor-beta 1-stimulated capillary organization in vitro. , 1997, The American journal of pathology.

[36]  P. Carmeliet,et al.  Angiogenesis in cancer and other diseases , 2000, Nature.

[37]  N. Opitz,et al.  NOSTRIN: A protein modulating nitric oxide release and subcellular distribution of endothelial nitric oxide synthase , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[38]  A. Ridley,et al.  Monocyte Adhesion and Spreading on Human Endothelial Cells Is Dependent on Rho-regulated Receptor Clustering , 1999, The Journal of cell biology.

[39]  Y. Mori,et al.  Differential roles of ICAM-1 and E-selectin in polymorphonuclear leukocyte-induced angiogenesis. , 2002, American journal of physiology. Cell physiology.

[40]  P. Carmeliet,et al.  Molecular mechanisms of blood vessel growth. , 2001, Cardiovascular research.

[41]  Hanjoong Jo,et al.  Compensatory Phosphorylation and Protein-Protein Interactions Revealed by Loss of Function and Gain of Function Mutants of Multiple Serine Phosphorylation Sites in Endothelial Nitric-oxide Synthase* , 2003, The Journal of Biological Chemistry.

[42]  A. Strosberg,et al.  Intercellular adhesion molecule 1 activation induces tyrosine phosphorylation of the cytoskeleton-associated protein cortactin in brain microvessel endothelial cells. , 1994, The Journal of biological chemistry.

[43]  S Amerini,et al.  Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P. , 1994, The Journal of clinical investigation.

[44]  D Zicha,et al.  A new direct-viewing chemotaxis chamber. , 1991, Journal of cell science.

[45]  K. Moore,et al.  Formation of nanomolar concentrations of S-nitroso-albumin in human plasma by nitric oxide. , 2001, Free radical biology & medicine.

[46]  E. Pluskota,et al.  Src Homology Domain 2-containing Tyrosine Phosphatase 2 Associates with Intercellular Adhesion Molecule 1 to Regulate Cell Survival* , 2000, The Journal of Biological Chemistry.

[47]  W. Kummer,et al.  NOSIP, a novel modulator of endothelial nitric oxide synthase activity , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[48]  P. Huang,et al.  Nitric oxide synthase modulates angiogenesis in response to tissue ischemia. , 1998, The Journal of clinical investigation.

[49]  A. Strosberg,et al.  Association of the cytoplasmic domain of intercellular-adhesion molecule-1 with glyceraldehyde-3-phosphate dehydrogenase and beta-tubulin. , 1996, European journal of biochemistry.

[50]  T. Oshima,et al.  H(2)O(2)-mediated permeability: role of MAPK and occludin. , 2000, American journal of physiology. Cell physiology.

[51]  R. Hoover,et al.  The Src‐cortactin pathway is required for clustering of E‐selectin and ICAM‐1 in endothelial cells , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[52]  Z. Radisavljevic,et al.  Vascular Endothelial Growth Factor Up-regulates ICAM-1 Expression via the Phosphatidylinositol 3 OH-kinase/AKT/Nitric Oxide Pathway and Modulates Migration of Brain Microvascular Endothelial Cells* , 2000, The Journal of Biological Chemistry.

[53]  T. Oshima,et al.  The role of p38 MAP kinase in hydrogen peroxide mediated endothelial solute permeability. , 2001, Endothelium : journal of endothelial cell research.

[54]  W. Sessa,et al.  Regulation of endothelium-derived nitric oxide production by the protein kinase Akt , 1999, Nature.

[55]  E L Ritman,et al.  Enhanced coronary vasa vasorum neovascularization in experimental hypercholesterolemia. , 1998, The Journal of clinical investigation.

[56]  G. Dunn,et al.  Analyzing chemotaxis using the Dunn direct-viewing chamber. , 1997, Methods in molecular biology.

[57]  R. Busse,et al.  Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation , 1999, Nature.

[58]  D. Power,et al.  Coordinated Control of Endothelial Nitric-oxide Synthase Phosphorylation by Protein Kinase C and the cAMP-dependent Protein Kinase* , 2001, The Journal of Biological Chemistry.

[59]  K. Hirata,et al.  Involvement of Endothelial Nitric Oxide in Sphingosine-1-Phosphate–Induced Angiogenesis , 2001 .