Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Future Articles
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
 Blood, 9 July 2009, Vol. 114, No. 2, pp. 318-327.
Prepublished online as a Blood First Edition Paper on May 6, 2009; DOI 10.1182/blood-2008-10-184457.

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Methods and Figures
Right arrow All Versions of this Article:
blood-2008-10-184457v1
114/2/318    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
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
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Google Scholar
Right arrow Articles by Dai, X.
Right arrow Articles by MacAry, P. A.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dai, X.
Right arrow Articles by MacAry, P. A.
Related Collections
Right arrow Immunobiology
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Table of Contents  |  Next Article next article arrow

IMMUNOBIOLOGY

Differential signal transduction, membrane trafficking, and immune effector functions mediated by Fc{gamma}RI versus Fc{gamma}RIIa

Xilei Dai1, Manikandan Jayapal2, Hwee Kee Tay2, Renji Reghunathan2, Gen Lin1, Chien Tei Too1, Yan Ting Lim1, Soh Ha Chan1, D. Michael Kemeny1, R. Andres Floto3, Kenneth G. C. Smith3, Alirio J. Melendez2,4, and Paul A. MacAry1

Departments of 1 Microbiology and 2 Physiology, National University of Singapore, Singapore; 3 Department of Medicine/CIMR University of Cambridge, Cambridge, United Kingdom; and 4 Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom

Receptors for the fragment crystallizable region of immunoglobulin-G (Fc{gamma}Rs) play an important role in linking the humoral and cellular arms of the immune response. In this study, we present a comprehensive functional comparison of 2 human Fc-receptors, Fc{gamma}RI and Fc{gamma}RIIa. Activation of Fc{gamma}RI results in a novel signaling cascade that links phospholipase D1 to sphingosine kinase-1 in U937 cells and primary human monocytes. This induces the expression of proinflammatory mediators and is associated with trafficking of immune complexes into human leukocyte antigen-DM positive antigen-processing compartments coupled with improved MHC class II–mediated antigen presentation to T lymphocytes. In contrast, activation of Fc{gamma}RIIa elicits signaling through phospholipase C{gamma}1, resulting in increases in intracellular calcium, activation of nicotinamide adenine dinucleotide phosphate-oxidative burst, and differential membrane trafficking combined with impaired antigen presentation and proinflammatory cytokine expression. These data provide a mechanistic insight into the disparate activities associated with Fc receptors in immunity, namely, reinforcement of immune responses through stimulation of proinflammatory signaling and antigen presentation, versus the maintenance of immunologic homeostasis through the noninflammatory clearance of immune complexes.


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




click for free articles
home about blood authors subscriptions permissions advertising public access contact us
  Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020