Abstract |
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.
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Authors | Abigail Woodfin, Christoph Andreas Reichel, Andrej Khandoga, Monica Corada, Mathieu-Benoit Voisin, Christoph Scheiermann, Dorian O Haskard, Elisabetta Dejana, Fritz Krombach, Sussan Nourshargh |
Journal | Blood
(Blood)
Vol. 110
Issue 6
Pg. 1848-56
(Sep 15 2007)
ISSN: 0006-4971 [Print] United States |
PMID | 17505016
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Cell Adhesion Molecules
- F11r protein, mouse
- Platelet Endothelial Cell Adhesion Molecule-1
- Receptors, Cell Surface
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Topics |
- Animals
- Antibodies, Monoclonal
(pharmacology)
- Cell Adhesion
- Cell Adhesion Molecules
(genetics, physiology)
- Cell Movement
(physiology)
- Disease Models, Animal
- Female
- Fluorescent Antibody Technique
- Leukocytes
(cytology, physiology)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Muscles
(cytology, metabolism)
- Neutrophils
(physiology)
- Platelet Endothelial Cell Adhesion Molecule-1
(genetics, physiology)
- Receptors, Cell Surface
(genetics, physiology)
- Reperfusion Injury
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