Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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A more recent version of this article appeared on March 1, 2007

Published online before print December 12, 2006
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0906553


Received for publication September 6, 2006.
Revised October 6, 2006.
Accepted for publication November 8, 2006.


Article

Transendothelial migration enhances integrin-dependent human neutrophil chemokinesis

Anjelica L. Gonzalez *@, Wafa El-Bjeirami *, Jennifer L. West {dagger}, Larry V. McIntire {ddagger}, and C. Wayne Smith *

*Section of Leukocyte Biology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA; {dagger}Department of Bioengineering, Rice University, Houston, Texas, USA; and {ddagger}Coulter Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, Atlanta, Georgia, USA

@ To whom correspondence should be addressed. E-mail: ag042775{at}bcm.tmc.edu.


   Abstract

Transendothelial migration of neutrophils induces phenotypic changes that influence the interactions of neutrophils with extravascular tissue components. To assess the influence of transmigration on neutrophil chemokinetic motility, we used polyethylene glycol hydrogels covalently modified with specific peptide sequences relevant to extracellular matrix proteins. We evaluated formyl-Met-Leu-Phe-stimulated human neutrophil motility on peptides Arg-Gly-Asp-Ser (RGDS) and TMKIIPFNRTLIGG (P2), alone and in combination. RGDS is a bioactive sequence found in a number of proteins, and P2 is a membrane-activated complex-1 (Mac-1) ligand located in the {gamma}-chain of the fibrinogen protein. We evaluated, via video microscopy, cell motility by measuring cell displacement from origin and total accumulated distance traveled and then calculated average velocity. Results indicate that although adhesion and shape change were supported by hydrogels containing RGD alone, motility was not. Mac-1-dependent motility was supported on hydrogels containing P2 alone. Motility was enhanced through combined presentation of RGD and P2, engaging Mac-1, {alpha}V{beta}3, and {beta}1 integrins. Naïve neutrophil motility on combined peptide substrates was dependent on Mac-1, and {alpha}4{beta}1 and {alpha}6{beta}1 contributed to speed and linear movement. Transmigrated neutrophil motility was dependent on {alpha}v{beta}3 and {alpha}5{beta}1, and {alpha}4{beta}1, {alpha}6{beta}1, and Mac-1 contributed to speed and linear motion. Together, the data demonstrate that efficient neutrophil migration, dependent on multi-integrin interaction, is enhanced after transendothelial migration.

Key Words: transmigration • {beta}1 integrins • inflammation • extracellular matrix • motility • {beta}2 integrin







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Copyright © 2006 by the Society for Leukocyte Biology.