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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.

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.
AuthorsAbigail Woodfin, Christoph Andreas Reichel, Andrej Khandoga, Monica Corada, Mathieu-Benoit Voisin, Christoph Scheiermann, Dorian O Haskard, Elisabetta Dejana, Fritz Krombach, Sussan Nourshargh
JournalBlood (Blood) Vol. 110 Issue 6 Pg. 1848-56 (Sep 15 2007) ISSN: 0006-4971 [Print] United States
PMID17505016 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Cell Adhesion Molecules
  • F11r protein, mouse
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Receptors, Cell Surface
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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