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The direction of migration of T-lymphocytes under flow depends upon which adhesion receptors are engaged

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The direction of migration of T-lymphocytes under flow depends upon which adhesion receptors are engaged

Content Provider	Royal Society of Chemistry (RSC)
Author	Anderson, Nicholas R. Dominguez, George A. Hammer, Daniel A.
Copyright Year	2015
Abstract	T-lymphocyte migration is important for homing, cell trafficking, and immune surveillance. T-lymphocytes express lymphocyte function-associated antigen-1 (LFA-1; αLβ2) and very late antigen-4 (VLA-4; α4β1), which bind to their cognate ligands, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). These adhesive interactions provide T-lymphocytes with the ability to withstand hemodynamic shear forces to facilitate adhesion and migration along the blood endothelium. Recently, it has been shown that T-lymphocytes will crawl upstream against the direction of flow on surfaces functionalized with ICAM-1. Here, we have investigated whether the identity of the receptor and the magnitude of its engagement affects the direction of T-lymphocyte migration under flow. We used microcontact printed ICAM-1 and VCAM-1 PDMS surfaces on which density and type of adhesion molecule can be tightly controlled and non-specific adhesion adequately blocked. Using a laminar flow chamber, we demonstrate that T-lymphocytes migrate either upstream or downstream dependent upon ligand type, ligand concentration and shear rate. T-lymphocytes were found to migrate upstream on ICAM-1 but downstream on VCAM-1 surfaces – a behavior unique to T-lymphocytes. By varying concentrations of ICAM-1 and VCAM-1, directed migration under flow was observed to be dependent upon the type and concentration of ligand. As shear rates increase, T-lymphocytes favor upstream migration when any ICAM-1 is present, even in the presence of substantial amounts of VCAM-1. Furthermore, a loss of cytoskeletal polarity was observed upon introduction of fluid flow with reorganization that is dependent upon ligand presentation. These results indicate that T-lymphocytes exhibit two different modes of motility – upstream or downstream – under fluid flow that depends on ligand composition and the shear rate.
Starting Page	345
Ending Page	355
Page Count	11
File Format	HTM / HTML PDF
ISSN	17579694
Volume Number	7
Issue Number	3
Journal	Integrative Biology
DOI	10.1039/c4ib00201f
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	T cell Lymphocyte function-associated antigen 1 Antigen VLA-4 Cell adhesion molecule ICAM-1 VCAM-1 Endothelium Laminar flow Ligand Shear rate
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Biophysics

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