JAM-A mediates neutrophil transmigration in a stimulus-specific manner in vivo: evidence for sequential roles for JAM-A and PECAM-1 in neutrophil transmigration.
Junctional adhesion molecule-A (JAM-A) is a transmembrane protein expressed at tight junctions of endothelial and epithelial cells and on the surface of platelets and leukocytes. The role of JAM-A in leukocyte transmigration in vivo was directly investigated by intravital microscopy using both a JAM-A-neutralizing monoclonal antibody (mAb) (BV-11) and JAM-A-deficient (knockout [KO]) mice. Leukocyte transmigration (but not adhesion) through mouse cremasteric venules as stimulated by interleukin 1beta (IL-1beta) or ischemia/reperfusion (I/R) injury was significantly reduced in wild-type mice treated with BV-11 and in JAM-A KO animals. In contrast, JAM-A blockade/genetic deletion had no effect on responses elicited by leukotriene B(4) (LTB(4)) or platelet-activating factor (PAF). Furthermore, using a leukocyte transfer method and mice deficient in endothelial-cell JAM-A, evidence was obtained for the involvement of endothelial-cell JAM-A in leukocyte transmigration mediated by IL-1beta. Investigation of the functional relationship between JAM-A and PECAM-1 (CD31) determined that dual blockade/deletion of these proteins does not lead to an inhibitory effect greater than that seen with blockade/deletion of either molecule alone. The latter appeared to be due to the fact that JAM-A and PECAM-1 can act sequentially to mediate leukocyte migration through venular walls in vivo.
Woodfin
Abigail
A
Cardiovascular Medicine Unit, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom.
Reichel
Christoph Andreas
CA
Khandoga
Andrej
A
Corada
Monica
M
Voisin
Mathieu-Benoit
MB
Scheiermann
Christoph
C
Haskard
Dorian O
DO
Dejana
Elisabetta
E
Krombach
Fritz
F
Nourshargh
Sussan
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D007962:Leukocytes / Q000166:cytology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009132:Muscles / Q000166:cytology / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D015427:Reperfusion Injury
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; C498686:F11r protein, mouse; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011956:Receptors, Cell Surface