| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Biology and
Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, and
Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund, London, United Kingdom
Correspondence: Joseph R. Woska, Jr., Department of Biology, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, CT 06877. E-mail: jwoska{at}rdg.boehringer-ingelheim.com
Lymphocyte function-associated antigen (LFA)-1/intercellular adhesion molecule (ICAM)-1 interactions mediate several important steps in the evolution of an immune response. LFA-1 is normally expressed in a quiescent state on the surface of leukocytes and interacts weakly with its ligands ICAM-1, -2, and -3. LFA-1 activity may be regulated by receptor clustering and by increasing the affinity of LFA-1 for its ligands. Affinity modulation of LFA-1 has been shown to occur via a conformational change in the LFA-1 heterodimer that can be detected by using monoclonal antibody 24 (mAb24). We have recently described a small-molecule antagonist of LFA-1, BIRT 377, that demonstrates selective in vitro and in vivo inhibition of LFA-1/ICAM-1-mediated binding events. We now demonstrate that BIRT 377 blocks the induction of the mAb24 reporter epitope on LFA-1 on the surface of SKW-3 cells treated with various agonists known to induce high-affinity LFA-1. These data imply that BIRT 377 exerts its inhibitory effects by preventing up-regulation of LFA-1 to its high-affinity conformation.
Key Words: adhesion molecules • inflammation • cell-cell interactions • FACS • integrin • mAb epitope
This article has been cited by other articles:
|
|
 |
|
  M. Shimaoka, M. Kim, E. H. Cohen, W. Yang, N. Astrof, D. Peer, A. Salas, A. Ferrand, and T. A. Springer AL-57, a ligand-mimetic antibody to integrin LFA-1, reveals chemokine-induced affinity up-regulation in lymphocytes PNAS, September 19, 2006; 103(38): 13991 - 13996. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Nagarajan, B. W. Stewart, and T. M. Badger Soy Isoflavones Attenuate Human Monocyte Adhesion to Endothelial Cell-Specific CD54 by Inhibiting Monocyte CD11a J. Nutr., September 1, 2006; 136(9): 2384 - 2390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Green, U. Y. Schaff, M. R. Sarantos, A. F. H. Lum, D. E. Staunton, and S. I. Simon Dynamic shifts in LFA-1 affinity regulate neutrophil rolling, arrest, and transmigration on inflamed endothelium Blood, March 1, 2006; 107(5): 2101 - 2111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Barnard, T. Igakura, Y. Tanaka, G. P. Taylor, and C. R.M. Bangham Engagement of specific T-cell surface molecules regulates cytoskeletal polarization in HTLV-1-infected lymphocytes Blood, August 1, 2005; 106(3): 988 - 995. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gunzer, C. Weishaupt, A. Hillmer, Y. Basoglu, P. Friedl, K. E. Dittmar, W. Kolanus, G. Varga, and S. Grabbe A spectrum of biophysical interaction modes between T cells and different antigen-presenting cells during priming in 3-D collagen and in vivo Blood, November 1, 2004; 104(9): 2801 - 2809. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Ustinov and E. F. Plow Delineation of the Key Amino Acids Involved in Neutrophil Inhibitory Factor Binding to the I-domain Supports a Mosaic Model for the Capacity of Integrin alpha Mbeta 2 to Recognize Multiple Ligands J. Biol. Chem., May 17, 2002; 277(21): 18769 - 18776. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
