The junctional adhesion molecule-C promotes neutrophil transendothelial migration in vitro and in vivo.
The third member of the family of junctional adhesion molecules (JAMs), JAM-3, also called JAM-C, was recently shown to be a novel counter-receptor on platelets for the leukocyte beta(2)-integrin Mac-1 (alphaMbeta(2), CD11b/CD18). Here, new functional aspects of the role of endothelial cell JAM-C were investigated. Endothelial cells express JAM-C, which is predominantly localized within junctions at interendothelial contacts, since it codistributes with a tight junction component, zonula occludens-1. Whereas JAM-C does not participate in neutrophil adhesion to endothelial cells, it mediates neutrophil transmigration in a Mac-1-dependent manner. In particular, inhibition of JAM-C significantly reduced neutrophil transendothelial migration, and the combination of JAM-C and platelet/endothelial cell adhesion molecule-1 blockade almost completely abolished neutrophil transendothelial migration in vitro. In vivo, inhibition of JAM-C with soluble mouse JAM-C resulted in a 50% reduction of neutrophil emigration in the mouse model of acute thioglycollate-induced peritonitis. Thus, JAM-C participates in neutrophil transmigration and thereby provides a novel molecular target for antagonizing interactions between vascular cells that promote inflammatory vascular pathologies.
Department of Internal Medicine I, University Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany. triantafyllos.chavakis@med.uni-heidelberg.de
Triantafyllos
T
Chavakis
Tanja
T
Keiper
Rachel
R
Matz-Westphal
Karin
K
Hersemeyer
Ulrich J
UJ
Sachs
Peter P
PP
Nawroth
Klaus T
KT
Preissner
Sentot
S
Santoso
D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000502:physiology*; D002465:Cell Movement; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D007136:Immunoglobulins / Q000737:chemistry / Q000502:physiology*; D066298:In Vitro Techniques; D007249:Inflammation; D062726:Junctional Adhesion Molecules; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D010538:Peritonitis / Q000473:pathology; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D062826:Zonula Occludens-1 Protein
D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C486723:Jam3 protein, mouse; D062726:Junctional Adhesion Molecules; D008565:Membrane Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D013755:Tetradecanoylphorbol Acetate