The Journal of Experimental Medicine
Avanti Polar Lipids, Inc.
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 557K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hafezi-Moghadam, A.
Right arrow Articles by Ley, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hafezi-Moghadam, A.
Right arrow Articles by Ley, K.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/1999/3/939/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 6, March 15, 1999 939-948

Articles

Relevance of L-selectin Shedding for Leukocyte Rolling In Vivo

Ali Hafezi-Moghadam and Klaus Ley

From the Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22908

The velocity of rolling leukocytes is thought to be determined by the expression of adhesion molecules and the prevailing wall shear stress. Here, we investigate whether rapid cleavage of L-selectin may be an additional physiologic regulatory parameter of leukocyte rolling. A unique protease in the membrane of leukocytes cleaves L-selectin after activation, resulting in L-selectin shedding. The hydroxamic acid–based metalloprotease inhibitor KD-IX-73-4 completely prevented L-selectin shedding in vitro and significantly decreased the rolling velocity of leukocytes in untreated wild-type C57BL/6 mice from 55 to 35 µm/s in vivo. When E-selectin was expressed on the endothelium (tumor necrosis factor [TNF]-{alpha} treatment 2.5–3 h before the experiment), rolling velocity was 4 µm/s and did not change after the application of KD-IX-73-4. However, KD-IX-73-4 decreased mean rolling velocity by 29% from 23 to 16 µm/s in E-selectin–deficient mice treated with TNF-{alpha}. The reduction of velocity caused by KD-IX-73-4 was immediate (<5 s) after injection of KD-IX-73-4 as shown by a novel method using a local catheter. These results establish a role for L-selectin shedding in regulating leukocyte rolling velocity in vivo.

Key Words: mouse • inflammation • protease inhibitor • trafficking • velocity

Address correspondence to Klaus Ley, Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908. Phone: 804-924-1722; Fax: 804-982-3870; E-mail: kfl3f{at}virginia.edu

Abbreviations used: HUVEC, human umbilical vein endothelial cell; PMN, polymorphonuclear granulocyte; SI, slower isomer (negative control).


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS