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J. Cell Biol., Volume 142, Number 1, July 13, 1998 117-127

Junctional Adhesion Molecule, a Novel Member of the Immunoglobulin Superfamily That Distributes at Intercellular Junctions and Modulates Monocyte Transmigration

Inés Martìn-Padura,* Susan Lostaglio,* Markus Schneemann,Dagger Lisa Williams,Dagger Maria Romano,* Paolo Fruscella,* Carla Panzeri,§ Antonella Stoppacciaro,parallel Luigi Ruco,parallel Antonello Villa,§ David Simmons,Dagger and Elisabetta Dejana*

* Istituto di Ricerche Farmacologiche Mario Negri, 20157 Milano, Italy; Dagger  Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, United Kingdom; § Dipartimento di Farmacologia, Universita degli Studi di Milano, and DIBIT, Milano, Italy 20129; and parallel  Universita' degli Studi La Sapienza, Dipartimento di Medicina Sperimentale e Patologia, 00161 Roma, Italy

Tight junctions are the most apical components of endothelial and epithelial intercellular cleft. In the endothelium these structures play an important role in the control of paracellular permeability to circulating cells and solutes. The only known integral membrane protein localized at sites of membrane-membrane interaction of tight junctions is occludin, which is linked inside the cells to a complex network of cytoskeletal and signaling proteins. We report here the identification of a novel protein (junctional adhesion molecule [JAM]) that is selectively concentrated at intercellular junctions of endothelial and epithelial cells of different origins. Confocal and immunoelectron microscopy shows that JAM codistributes with tight junction components at the apical region of the intercellular cleft. A cDNA clone encoding JAM defines a novel immunoglobulin gene superfamily member that consists of two V-type Ig domains. An mAb directed to JAM (BV11) was found to inhibit spontaneous and chemokine-induced monocyte transmigration through an endothelial cell monolayer in vitro. Systemic treatment of mice with BV11 mAb blocked monocyte infiltration upon chemokine administration in subcutaneous air pouches. Thus, JAM is a new component of endothelial and epithelial junctions that play a role in regulating monocyte transmigration.

Key words: endotheliumepitheliummonocytetight junctionsinflammation


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