Vascular endothelial-cadherin is an important determinant of microvascular integrity in vivo.

In the present paper, we characterize an antibody, mAb BV13, directed to mouse vascular endothelial (VE)-cadherin, a major adhesive protein of interendothelial adherens junctions. When added to cultured endothelial cells, BV13 induces a redistribution of VE-cadherin from intercellular junctions. VE-cadherin redistribution did not change the localization of platelet endothelial cell adhesion molecule or tight junction markers such as zonula occludens 1, cingulin, and junctional adhesion molecule. Intravenous administration of mAb BV13 induced a concentration- and time-dependent increase in vascular permeability in heart and lungs. By electron microscopy, interstitial edema and accumulation of mixed types of inflammatory cells in heart and lungs were observed. Injection of (rhodamine-labeled) Ricinus communis I lectin showed focal spots of exposed basement membrane in the alveolar capillaries and in some larger pulmonary vessels. These data indicate that VE-cadherin is required for vascular integrity and normal organ functions.

[1]  E. Dejana,et al.  Junctional Adhesion Molecule, a Novel Member of the Immunoglobulin Superfamily That Distributes at Intercellular Junctions and Modulates Monocyte Transmigration , 1998, The Journal of cell biology.

[2]  Kazushi Fujimoto,et al.  Claudin-1 and -2: Novel Integral Membrane Proteins Localizing at Tight Junctions with No Sequence Similarity to Occludin , 1998, The Journal of cell biology.

[3]  D. Predescu,et al.  Transcytosis of alpha1-acidic glycoprotein in the continuous microvascular endothelium. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[4]  D. Hanahan,et al.  Cationic liposomes target angiogenic endothelial cells in tumors and chronic inflammation in mice. , 1998, The Journal of clinical investigation.

[5]  G. Breier,et al.  Vascular Endothelial Growth Factor Induces Endothelial Fenestrations In Vitro , 1998, The Journal of cell biology.

[6]  M. Lampugnani,et al.  Interendothelial junctions: structure, signalling and functional roles. , 1997, Current opinion in cell biology.

[7]  S Esser,et al.  Cell confluence regulates tyrosine phosphorylation of adherens junction components in endothelial cells. , 1997, Journal of cell science.

[8]  C. Garlanda,et al.  A general strategy for isolation of endothelial cells from murine tissues. Characterization of two endothelial cell lines from the murine lung and subcutaneous sponge implants. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[9]  E. Dejana,et al.  Targeted null-mutation in the vascular endothelial-cadherin gene impairs the organization of vascular-like structures in embryoid bodies. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[10]  V. Hinsbergh.  Endothelial Permeability for Macromolecules Mechanistic Aspects of Pathophysiological Modulation , 1997 .

[11]  C. V. Van Itallie,et al.  Occludin confers adhesiveness when expressed in fibroblasts. , 1997, Journal of cell science.

[12]  S. Bolling,et al.  Mediators of ischemia-reperfusion injury of rat lung. , 1997, The American journal of pathology.

[13]  D. Vestweber,et al.  VE-cadherin antibody accelerates neutrophil recruitment in vivo. , 1997, Journal of cell science.

[14]  L. Rubin,et al.  Cell adhesion, cell junctions and the blood—brain barrier , 1996, Current Opinion in Neurobiology.

[15]  P. Ward,et al.  Requirement and role of C5a in acute lung inflammatory injury in rats. , 1996, The Journal of clinical investigation.

[16]  H. Aberle,et al.  Cadherin‐catenin complex: Protein interactions and their implications for cadherin function , 1996, Journal of cellular biochemistry.

[17]  M. Lampugnani,et al.  Thrombin-induced increase in endothelial permeability is associated with changes in cell-to-cell junction organization. , 1996, Arteriosclerosis, thrombosis, and vascular biology.

[18]  B. Gumbiner,et al.  Cell Adhesion: The Molecular Basis of Tissue Architecture and Morphogenesis , 1996, Cell.

[19]  F. Breviario,et al.  Molecular cloning and expression of murine vascular endothelial-cadherin in early stage development of cardiovascular system. , 1996, Blood.

[20]  H. Dvorak,et al.  The vesiculo‐vacuolar organelle (VVO): a distinct endothelial cell structure that provides a transcellular pathway for macromolecular extravasation , 1996, Journal of leukocyte biology.

[21]  F. Breviario,et al.  Catenin-dependent and -independent Functions of Vascular Endothelial Cadherin (*) , 1995, The Journal of Biological Chemistry.

[22]  M. Corada,et al.  Functional properties of human vascular endothelial cadherin (7B4/cadherin-5), an endothelium-specific cadherin. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[23]  M. Corada,et al.  Endothelial cell‐to‐cell junctions , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[24]  B. Geiger,et al.  The molecular organization of endothelial cell to cell junctions: differential association of plakoglobin, beta-catenin, and alpha- catenin with vascular endothelial cadherin (VE-cadherin) , 1995, The Journal of cell biology.

[25]  C. Garlanda,et al.  Progressive growth in immunodeficient mice and host cell recruitment by mouse endothelial cells transformed by polyoma middle-sized T antigen: implications for the pathogenesis of opportunistic vascular tumors. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[26]  B. Geiger,et al.  Spatial and temporal relationships between cadherins and PECAM-1 in cell-cell junctions of human endothelial cells , 1994, The Journal of cell biology.

[27]  C. Garlanda,et al.  Monoclonal antibodies specific for endothelial cells of mouse blood vessels. Their application in the identification of adult and embryonic endothelium. , 1994, European journal of cell biology.

[28]  A. Mantovani,et al.  A novel mechanism of colon carcinoma cell adhesion to the endothelium triggered by beta 1 integrin chain. , 1994, The Journal of biological chemistry.

[29]  M. Itoh,et al.  Occludin: a novel integral membrane protein localizing at tight junctions , 1993, The Journal of cell biology.

[30]  R. G. Anderson,et al.  Caveolae: where incoming and outgoing messengers meet. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[31]  James M. Anderson,et al.  The structure and regulation of tight junctions. , 1993, Current opinion in cell biology.

[32]  M. Takeichi.  Cadherins in cancer: implications for invasion and metastasis. , 1993, Current opinion in cell biology.

[33]  M. Lampugnani,et al.  A novel endothelial-specific membrane protein is a marker of cell-cell contacts , 1992, The Journal of cell biology.

[34]  C. Power,et al.  Molecular cloning of CD31, a putative intercellular adhesion molecule closely related to carcinoembryonic antigen , 1990, The Journal of experimental medicine.

[35]  B. Geiger,et al.  Cingulin: characterization and localization. , 1989, Journal of cell science.

[36]  S. Weiss.  Tissue destruction by neutrophils. , 1989, The New England journal of medicine.

[37]  Benjamin Geiger,et al.  Cingulin, a new peripheral component of tight junctions , 1988, Nature.

[38]  James M. Anderson,et al.  Characterization of ZO-1, a protein component of the tight junction from mouse liver and Madin-Darby canine kidney cells , 1988, The Journal of cell biology.

[39]  Osamu Uyama,et al.  Quantitative Evaluation of Vascular Permeability in the Gerbil Brain after Transient Ischemia Using Evans Blue Fluorescence , 1988, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[40]  J. G. Michael,et al.  C3 dependent, C5 independent immune complex glomerulopathy in the mouse. , 1988, Laboratory investigation; a journal of technical methods and pathology.

[41]  J. Siliciano,et al.  Identification of ZO-1: a high molecular weight polypeptide associated with the tight junction (zonula occludens) in a variety of epithelia , 1986, The Journal of cell biology.

[42]  H. Müller-Eberhard,et al.  Depletion of plasma complement in vivo by a protein of cobra venom: its effect on various immunologic reactions. , 1970, Journal of immunology.

[43]  E. Dejana,et al.  Perspectives Series: Cell Adhesion in Vascular Biology Endothelial Adherens Junctions: Implications in the Control of Vascular Permeability and Angiogenesis , 1996 .

[44]  E. Dejana,et al.  Thrombin-induced endothelial cell dysfunction. , 1994, British medical bulletin.

[45]  B. Lucchesi,et al.  Modulation of leukocyte-mediated myocardial reperfusion injury. , 1990, Annual review of physiology.

[46]  E. Harlow,et al.  Antibodies: A Laboratory Manual , 1988 .

[47]  W. Rössner,et al.  [Quantitative determination of the permeability of the so-called blood-brain barrier of Evans blue (T 1824)]. , 1966, Medicina et pharmacologia experimentalis. International journal of experimental medicine.