MolPharm

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Molecular Pharmacology Fast Forward
First published on October 27, 2008; DOI: 10.1124/mol.108.051169

0026-895X/09/7502-355-362$20.00
Mol Pharmacol 75:355-362, 2009

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
mol.108.051169v1
75/2/355    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Weitz-Schmidt, G.
Right arrow Articles by Riek, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Weitz-Schmidt, G.
Right arrow Articles by Riek, S.

Allosteric LFA-1 Inhibitors Modulate Natural Killer Cell Function

Gabriele Weitz-Schmidt, Stéphanie Chreng, and Simone Riek

Department of Autoimmunity, Transplantation, and Inflammation, Novartis Institutes for BioMedical Research, Basel, Switzerland

Natural killer (NK) cells are believed to play an important role in a variety of disease pathologies, including transplant rejection and autoimmunity. None of the therapeutic modalities currently available are known to potently interfere with NK cell activity. Here we demonstrate for the first time that low molecular weight inhibitors of the integrin lymphocyte function-associated antigen-1 (LFA-1) readily block NK cell adhesion, activation, and NK cell-mediated cytolysis in vitro, in contrast to other immunosuppressive agents. These effects were independent of the type of allosteric mechanism by which LFA-1 inhibition was achieved. In addition, we describe a simple, nonradioactive whole-blood assay that should be suitable to monitor NK cell activation in clinical practice. Taken together, our study underlines the importance of LFA-1 in NK cell effector functions and indicates that allosteric LFA-1 inhibitors may become important tools to further elucidate the therapeutic potential of NK cell modulation in immunological diseases.

Received for publication August 7, 2008.

Accepted for publication October 27, 2008.

Address correspondence to: Dr. Gabriele Weitz-Schmidt, Department of Autoimmunity, Transplantation and Inflammation, Novartis Institutes for BioMedical Research, WSJ-386.528, CH-4002 Basel, Switzerland. E-mail: gabriele.weitz{at}novartis.com




This article has been cited by other articles:


Home page
 Antimicrob. Agents Chemother.Home page
M. R. Tardif, C. Gilbert, S. Thibault, J.-F. Fortin, and M. J. Tremblay
LFA-1 Antagonists as Agents Limiting Human Immunodeficiency Virus Type 1 Infection and Transmission and Potentiating the Effect of the Fusion Inhibitor T-20
Antimicrob. Agents Chemother., November 1, 2009; 53(11): 4656 - 4666.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2009 by the American Society for Pharmacology and Experimental Therapeutics