The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 370K)
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 CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Palframan, R. T.
Right arrow Articles by Rankin, S. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Palframan, R. T.
Right arrow Articles by Rankin, S. M.
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, 0022-1007/1998/11/1621/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 9, November 2, 1998 1621-1632

Articles

Mechanisms of Acute Eosinophil Mobilization from the Bone Marrow Stimulated by Interleukin 5: The Role of Specific Adhesion Molecules and Phosphatidylinositol 3-Kinase

Roger T. Palframan*, Paul D. Collins*, Nicholas J. Severs{ddagger}, Stephen Rothery{ddagger}, Timothy J. Williams*, and Sara M. Rankin*

From the * Leukocyte Biology, Division of Biomedical Sciences, Imperial College School of Medicine, Sir Alexander Fleming Building, South Kensington, London SW7 2AZ, United Kingdom; and {ddagger} Cardiac Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, United Kingdom

Mobilization of bone marrow eosinophils is a critical early step in their trafficking to the lung during allergic inflammatory reactions. We have shown previously that the cytokine interleukin (IL)-5, generated during an allergic inflammatory reaction in the guinea pig, acts systemically to mobilize eosinophils from the bone marrow. Here, we have investigated the mechanisms underlying this release process. Examination by light and electron microscopy revealed the rapid migration of eosinophils from the hematopoietic compartment and across the bone marrow sinus endothelium in response to IL-5. Using an in situ perfusion system of the guinea pig hind limb, we showed that IL-5 stimulated a dose-dependent selective release of eosinophils from the bone marrow. Eosinophils released from the bone marrow in response to IL-5 expressed increased levels of β2 integrin and a decrease in L-selectin, but no change in {alpha}4 integrin levels. A β2 integrin–blocking antibody markedly inhibited the mobilization of eosinophils from the bone marrow stimulated by IL-5. In contrast, an {alpha}4 integrin blocking antibody increased the rate of eosinophil mobilization induced by IL-5. In vitro we demonstrated that IL-5 stimulates the selective chemokinesis of bone marrow eosinophils, a process markedly inhibited by two structurally distinct inhibitors of phosphatidylinositol 3-kinase, wortmannin and LY294002. Wortmannin was also shown to block eosinophil release induced by IL-5 in the perfused bone marrow system. The parallel observations on the bone marrow eosinophil release process and responses in isolated eosinophils in vitro suggest that eosinophil chemokinesis is the driving force for release in vivo and that this release process is regulated by {alpha}4 and β2 integrins acting in opposite directions.

Key Words: eosinophil • bone marrow • integrin • phosphatidylinositol 3-kinase • interleukin 5

Address correspondence to S.M. Rankin, Leukocyte Biology, Division of Biomedical Sciences, Imperial College School of Medicine, Sir Alexander Fleming Building, South Kensington, London SW7 2AZ, UK. Phone: 44-171-594-3172; Fax: 44-171-594-3002; E-mail: s.rankin{at}ic.ac.uk

Abbreviations used: PI 3-kinase, phosphatidylinositol 3-kinase; p70S6K, p70 S6-kinase; VCAM-1, vascular cell adhesion molecule 1; VLA4, very late antigen 4.


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?




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