en
Scientific article
English

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

Published inBlood, vol. 110, no. 6, p. 1848-1856
Publication date2007
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.

Keywords
  • 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
Affiliation Not a UNIGE publication
Citation (ISO format)
WOODFIN, Abigail et al. 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. In: Blood, 2007, vol. 110, n° 6, p. 1848–1856. doi: 10.1182/blood-2006-09-047431
Main files (1)
Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal0006-4971
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