Junctional adhesion molecule-A-deficient polymorphonuclear cells show reduced diapedesis in peritonitis and heart ischemia-reperfusion injury.
Junctional Adhesion Molecule-A (JAM-A) is a transmembrane adhesive protein expressed at endothelial junctions and in leukocytes. Here we report that JAM-A is required for the correct infiltration of polymorphonuclear leukocytes (PMN) into an inflamed peritoneum or in the heart upon ischemia-reperfusion injury. The defect was not observed in mice with an endothelium-restricted deficiency of the protein but was still detectable in mice transplanted with bone marrow from JAM-A(-/-) donors. Microscopic examination of mesenteric and heart microvasculature of JAM-A(-/-) mice showed high numbers of PMN adherent on the endothelium or entrapped between endothelial cells and the basement membrane. In vitro, in the absence of JAM-A, PMN adhered more efficiently to endothelial cells and basement membrane proteins, and their polarized movement was strongly reduced. This paper describes a nonredundant role of JAM-A in controlling PMN diapedesis through the vessel wall.
Corada
Monica
M
Fondazione Italiana per la Ricerca sul Cancro, Institute of Molecular Oncology, 20139 Milan, Italy.
Chimenti
Stefano
S
Cera
Maria Rosaria
MR
Vinci
Maria
M
Salio
Monica
M
Fiordaliso
Fabio
F
De Angelis
Noeleen
N
Villa
Antonello
A
Bossi
Mario
M
Staszewsky
Lidia I
LI
Vecchi
Annunciata
A
Parazzoli
Dario
D
Motoike
Toshiyuki
T
Latini
Roberto
R
Dejana
Elisabetta
E
D000818:Animals; D016026:Bone Marrow Transplantation; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000172:deficiency*; D002465:Cell Movement / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009504:Neutrophils / Q000378:metabolism* / Q000648:ultrastructure; D010538:Peritonitis / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism*
D015815:Cell Adhesion Molecules