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

Blood. 2007 Sep 15;110(6):1848-56. doi: 10.1182/blood-2006-09-047431. Epub 2007 May 15.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Cell Adhesion
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / physiology*
  • Cell Movement / physiology*
  • Disease Models, Animal
  • Female
  • Fluorescent Antibody Technique
  • Leukocytes / cytology
  • Leukocytes / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscles / cytology
  • Muscles / metabolism
  • Neutrophils / physiology*
  • Platelet Endothelial Cell Adhesion Molecule-1 / genetics
  • Platelet Endothelial Cell Adhesion Molecule-1 / physiology*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / physiology*
  • Reperfusion Injury


  • Antibodies, Monoclonal
  • Cell Adhesion Molecules
  • F11r protein, mouse
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Receptors, Cell Surface