Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration.
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.
Martìn-Padura
I
I
Istituto di Ricerche Farmacologiche Mario Negri, 20157 Milano, Italy. ines@irfmn.mnegri.it
Lostaglio
S
S
Schneemann
M
M
Williams
L
L
Romano
M
M
Fruscella
P
P
Panzeri
C
C
Stoppacciaro
A
A
Ruco
L
L
Villa
A
A
Simmons
D
D
Dejana
E
E
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000941:Antigens / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001483:Base Sequence; D019556:COS Cells; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004727:Endothelium / Q000166:cytology; D004847:Epithelial Cells / Q000378:metabolism; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D062726:Junctional Adhesion Molecules; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D012867:Skin / Q000276:immunology; D019108:Tight Junctions / Q000378:metabolism*; D014162:Transfection
D000911:Antibodies, Monoclonal; D000941:Antigens; D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D007136:Immunoglobulins; D062726:Junctional Adhesion Molecules