TNF-alpha and IFN-gamma promote lymphocyte adhesion to endothelial junctional regions facilitating transendothelial migration

Justyna Jaczewska, Midhat H. Abdulreda, Chi Y. Yau, Martin M. Schmitt, Irene Schubert, Per-Olof Berggren, Christian Weber, Rory R. Koenen, Vincent T. Moy, Ewa P. Wojcikiewicz*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

29 Citations (Web of Science)

Abstract

JAM-A redistribution on TNF-- and IFN--treated endothelium promotes regions of enhanced adhesion measured by AFM that facilitate lymphocyte TEM. Inflammatory conditions induce redistribution of junctional adhesion receptors toward the apical regions of endothelial cells promoting lymphocyte TEM. Much of the molecular structures of TEM have been revealed; however, the biophysical mechanisms underlying this process remain to be fully elucidated. Here, we used immunofluorescence microscopy and AFM to study endothelial distribution of adhesion molecules upon lymphocyte activation and transmigration. Our immunofluorescence results revealed redistribution of JAM-A and PECAM-1 but not ICAM-1 or VCAM-1 toward the apical junctional regions of HUVECs following a 6-h stimulation with TNF- and IFN-. Consistently, our SCFS studies revealed that Jurkat cell adhesion to stimulated HUVEC monolayers was significantly greater in junctional regions. Enhanced adhesion was mediated mostly by JAM-A receptors. Further AFM adhesion mapping of the homophilic JAM-A/JAM-A interaction on the surfaces of HUVECs revealed a greater number of JAM-A receptors available for binding along junctional regions after TNF- and IFN- stimulation. Our data reveal for the first time that adhesion hot spots of JAM-A receptors are involved in initiating lymphocyte TEM under inflammatory conditions.
Original languageEnglish
Pages (from-to)265-274
JournalJournal of Leukocyte Biology
Volume95
Issue number2
DOIs
Publication statusPublished - Feb 2014

Keywords

  • atomic force microscopy
  • immunofluorescence imaging
  • junctional adhesion molecule-A
  • single-cell force spectroscopy

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