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ECM interactions with neutrophil integrins regulate cell activity: An engineering approach to studying cell motility in inflammation
Author(s) -
GonzalezSimon Anjelica Leticia,
West Jennifer L,
McIntire Larry V,
Smith C Wayne
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1080-d
Subject(s) - integrin , motility , microbiology and biotechnology , cell adhesion , integrin alpha m , extracellular matrix , chemistry , adhesion , cell adhesion molecule , receptor , cell , biology , biochemistry , organic chemistry
The objective of this work was to define specific integrin/peptide interactions that support and induce neutrophil motility in 2‐D and evaluate related functional changes between naïve and transmigrated neutrophils. Methods were based on the use of a mimetic of extracellular matrix (ECM) to evaluate neutrophil integrin mediated motility. We used an inert polyethylene glycol (PEG) hydrogel, made bioactive by including peptide sequences. The hydrogel promotes interaction of human neutrophils with peptide sequences RGDS, a ligand for a4, a5 and b3 integrins, and TMKIIPFNRLTIGG (TMK), a fibrinogen derived ligand for Mac‐1 integrin. Our findings show that ECM domains that support adhesion do not necessarily facilitate motility. Integrins avb3, a4b1, a5b1, and a6b1 interacting with the RGDS do not provide sufficient signals nor mechanical means to mediate motility, though they do support adhesion and spreading. The Mac‐1 integrin interacting with the TMK peptide was able to support cell adhesion and mediate slow motility, but not cell spreading. Multi‐integrin interactions with combined peptides in the ECM mimetic exhibited enhanced adhesion, cell spreading, and motility. Increase in receptor expression and activation as a result of neutrophil migration across stimulated endothelium results in activity that is more dynamic than the activity of naive cells.