Published 20 December 2004. doi:10.1084/jem.20040965
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 12, 1571-1580
Coordinated Redistribution of Leukocyte LFA-1 and Endothelial Cell ICAM-1 Accompany Neutrophil Transmigration
Sunil K. Shaw1,
Shuo Ma1,
Michael B. Kim1,
Ravi M. Rao1,
Charles U. Hartman1,
Richard M. Froio1,
Lin Yang1,
Todd Jones1,
Yuan Liu2,
Asma Nusrat2,
Charles A. Parkos2, and
F. William Luscinskas1
1 Department of Pathology, Center for Excellence in Vascular Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115
2 Department of Pathology and Laboratory Medicine, Division of Gastrointestinal Pathology, Emory University, Atlanta, GA 30322
Address correspondence to F. William Luscinskas, Dept. of Pathology, Center for Excellence in Vascular Biology, Brigham and Women's Hospital and Harvard Medical School, 77 Louis Pasteur Ave., Boston, MA 02115. Phone: (617) 525-4337; Fax: (617) 525-4333; email: fluscinskas{at}rics.bwh.harvard.edu
The leukocyte integrin lymphocyte function-associated antigen 1 (LFA-1) and its endothelial ligand intercellular adhesion molecule (ICAM)-1 play an important role in transmigration as demonstrated by in vivo and in vitro models of inflammation. Despite the prominent role, little is known concerning the distribution and dynamic behavior of these adhesion molecules during leukocyte transmigration. Therefore, we examined the spatial and temporal distribution of LFA-1 on neutrophils actively transmigrating tumor necrosis factor-
activated human umbilical vein endothelial monolayers under shear flow. Upon neutrophil arrest, LFA-1 was evenly distributed. However, once neutrophils initiated transmigration, LFA-1 rapidly redistributed to form a ringlike cluster at the neutrophilendothelial junctional interface through which transmigration occurred. As transmigration was completed, LFA-1 redistributed to the neutrophil uropod. Endothelial ICAM-1 and JAM-A both colocalized with the ringlike LFA-1 cluster. Further analysis of PMA-stimulated neutrophils, which increase mobility of LFA-1, showed a rapid redistribution of LFA-1 and ICAM-1, but not endothelial JAM-A. Thus, endothelial JAM-A does not appear to contribute to adhesion or transmigration in this system. This is the first demonstration that neutrophil LFA-1 rapidly redistributes to form a ringlike structure that coclusters with endothelial ICAM-1 as the neutrophil transmigrates.
Key Words: inflammation diapedesis integrins adhesion molecules imaging
S.K. Shaw and S. Ma contributed equally to this work.
Abbreviations used in this paper: DIC, differential interference contrast; HUVEC, human umbilical vein endothelial cell; ICAM, intercellular adhesion molecule.

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