In:
Journal of Leukocyte Biology, Oxford University Press (OUP), Vol. 70, No. 2 ( 2001-08-01), p. 329-334
Abstract:
Lymphocyte function-associated antigen(LFA)-1/intercellular adhesion molecule (ICAM)-1interactions mediate several important steps in the evolution of animmune response. LFA-1 is normally expressed in a quiescent state onthe surface of leukocytes and interacts weakly with its ligands ICAM-1,-2, and -3. LFA-1 activity may be regulated by receptor clustering andby increasing the affinity of LFA-1 for its ligands. Affinitymodulation of LFA-1 has been shown to occur via a conformational changein the LFA-1 heterodimer that can be detected by using monoclonalantibody 24 (mAb24). We have recently described a small-moleculeantagonist of LFA-1, BIRT 377, that demonstrates selective in vitro andin vivo inhibition of LFA-1/ICAM-1-mediated binding events. We nowdemonstrate that BIRT 377 blocks the induction of the mAb24 reporterepitope on LFA-1 on the surface of SKW-3 cells treated with variousagonists known to induce high-affinity LFA-1. These data imply thatBIRT 377 exerts its inhibitory effects by preventing up-regulation ofLFA-1 to its high-affinity conformation.
Type of Medium:
Online Resource
ISSN:
0741-5400
,
1938-3673
DOI:
10.1189/jlb.70.2.329
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2001
detail.hit.zdb_id:
2026833-6
SSG:
12
Permalink
