Abstract:
:Integrin-mediated adhesion of circulating neutrophils to endothelium during inflammation involves multiple adhesion molecules on both neutrophils and endothelium. Most studies of neutrophil adhesion have focused on adhesion to ICAM-1 (mediated by beta(2) integrins), but interaction with the endothelial ligand vascular cell adhesion molecule 1 (VCAM-1) may also play a role in neutrophil adhesion to activated endothelium. In this study we demonstrate significant adhesion between neutrophils and VCAM-1 mediated by beta(1) integrins, principally via alpha(4)beta(1) (VLA-4). We characterize the dynamics of adhesion in terms of rate constants for a two-step bond formation process, the first involving juxtaposition of active molecules with substrate and the second involving bond formation. The results indicate that the first step is rate limiting for VLA-4-VCAM-1 interactions. Changing divalent cation composition affects these coefficients, implicating molecular conformational changes as a key step in the process.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
Lomakina EB,Waugh REdoi
10.1016/j.bpj.2008.10.001subject
Has Abstractpub_date
2009-01-01 00:00:00pages
276-84issue
1eissn
0006-3495issn
1542-0086pii
S0006-3495(08)00016-7journal_volume
96pub_type
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