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Elucidating the Kinetics of LFA‐1 and Mac‐1 Sequential Binding to ICAM‐1 under Shear Conditions
Author(s) -
Eniola Omolola,
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
Subject(s) - lymphocyte function associated antigen 1 , adhesion , biophysics , receptor–ligand kinetics , kinetics , microbiology and biotechnology , chemistry , cell adhesion , icam 1 , endothelium , biology , receptor , biochemistry , endocrinology , physics , quantum mechanics , organic chemistry
LFA‐1 and Mac‐1 are the integrins involved in the firm arrest of leukocytes to the endothelium during inflammation response. Previous work using a cone‐plate viscometer showed that the adhesion kinetics of LFA‐1 and Mac‐1 varies with shear rate and that LFA‐1 binding was transient, lasting ~2 min, while Mac‐1 sustained longer adhesion. This work suggests that LFA‐1 binding is necessary for Mac‐1 adhesion and supports the notion that LFA‐1 and Mac‐1 binding to ICAM‐1 is a cooperative and sequential process. While this work highlights important shear dependent kinetics of LFA‐1 and Mac‐1 with their ligands, it does not accurately mimic the in vivo neutrophil encounter with the endothelium. Furthermore, not much has been done to fully characterize the suggested sequential binding of LFA‐1 and Mac‐1 to ICAM‐1. Here, we explored the adhesion of FMLP stimulated human neutrophils to mouse L‐cells co‐transfected with human E‐selectin and ICAM‐1 in a parallel plate flow chamber in the presence or absence of function blocking antibodies to LFA‐1 and/or Mac‐1. Our results show that LFA‐1 mediated adhesion of neutrophils in laminar flow is transient lasting up to 1 min while Mac‐1 mediated adhesion serves to stabilize firm adhesion. Furthermore, the dependence of Mac‐1 mediated firm adhesion on initial LFA‐1/ICAM‐1 interaction increases with shear stress where there are insignificant differences in the level of Mac‐1 mediated firm adhesion in the presence or absence of LFA‐1 interactions at low wall shear stresses.