Coordinated redistribution of leukocyte LFA-1 and endothelial cell ICAM-1 accompany neutrophil transmigration

Sunil K. Shaw, Shuo Ma, Michael B. Kim, Ravi M. Rao, Charles U. Hartman, Richard M. Froio, Lin Yang, Todd Jones, Yuan Liu, Asma Nusrat, Charles A. Parkos, F. William Luscinskas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

174 Scopus citations

Abstract

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-α- 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 neutrophil-endothelial 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.

Original languageEnglish (US)
Pages (from-to)1571-1580
Number of pages10
JournalJournal of Experimental Medicine
Volume200
Issue number12
DOIs
StatePublished - Dec 20 2004

Keywords

  • Adhesion molecules
  • Diapedesis
  • Imaging
  • Inflammation
  • Integrins

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Coordinated redistribution of leukocyte LFA-1 and endothelial cell ICAM-1 accompany neutrophil transmigration'. Together they form a unique fingerprint.

Cite this