Journal
BLOOD
Volume 109, Issue 4, Pages 1381-1386Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2006-07-032995
Keywords
-
Categories
Funding
- NHLBI NIH HHS [R01 HL073714, HL073714, R01 HL060528] Funding Source: Medline
Ask authors/readers for more resources
Lymphocyte extravasation requires that emigrating cells process chemoattractant signals, typically mediated by chemokines, encountered on endothelial surface (apical) and subendothelial (basal) compartments. These signals are delivered under conditions of hemodynamic shear, a fundamental feature of all physiologic leukocyte-endothelial interactions. To analyze lymphocyte responsiveness to spatially distributed chemokines and their effects on transendothelial migration (TEM) under hydrodynamic shear, we constructed a transwell-based flow assay. We observed that the inflammatory chemokine CCL5 (RANTES) induces negligible human T-cell migration across inflamed human umbilical vascular endothelial cells (HUVECs) when displayed alone in the subendothelial compartment under static or hemodynamic shear conditions or when combined with apical CXCL12 (SDF-1 alpha) under static conditions. However, under shear stress, T cells encountering apically presented CXCL12 were primed to undergo robust LFA-1-dependent TEM toward subendothelial CCL5. Notably, locomotive T cells arriving at endothelial junctions were retained and extended pseudopodia into and through the junctions, thereby increasing sensitivity to subendothelial CCLS. These findings provide the first evidence that lymphocytes integrate, conditional to shear forces, permissive apical chemokine deposits, and integrin engagement signals, resulting in morphologic changes and amplified chemotaxis to an otherwise weak subendothelial chemokine signal.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available