help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on October 13, 2005, doi:10.1165/rcmb.2005-0126OC

Am. J. Respir. Cell Mol. Biol., Volume 34, Number 2, February 2006, 233-241

A more recent version of this article appeared on February 1, 2006
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2005-0126OCv1
34/2/233    most recent
Right arrow Alert me when this article is cited
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
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rahaman, M.
Right arrow Articles by Walsh, M.-T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rahaman, M.
Right arrow Articles by Walsh, M.-T.

Submitted on April 7, 2005
Revised on October 7, 2005

Neutrophil Sphingosine 1-phosphate and Lysophosphatidic Acid Receptors in Pneumonia

Matiur Rahaman1, Richard W Costello1*, Kristen E Belmonte2, Samir S Gendy1, and Marie-Therese Walsh1

1 Department of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland, 2 GlaxoSmithKline, Respiratory and Inflammation Centre of Excellence for Drug Discovery, PA, USA

* To whom correspondence should be addressed. E-mail: rcostello{at}rcsi.ie.

The phospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) act via transmembrane receptors S1P 1-5 and LPA 1-3 respectively. Both have been implicated in inflammatory responses. S1P and LPA receptor profiles on neutrophils of patients with pneumonia compared to healthy subjects were determined by polymerase chain reaction and Western blotting. Chemotaxis studies were carried out to assess functional differences. S1P or LPA receptors were immunoprecipitated from neutrophils to assess receptor heterodimerisation with CXCR1, an interleukin-8 receptor, by Western blotting. Receptors S1P 1, 4 and 5 and LPA 2 were expressed on neutrophils from both subject groups but S1P 3 and LPA 1 receptor expression was mainly confined to neutrophils of pneumonia patients. Chemotaxis of neutrophils from pneumonia patients compared to control subjects was significantly increased in response to both S1P and LPA. Pre-treatment with S1P or LPA reduced interleukin-8-induced neutrophil chemotaxis and transcriptional expression of the CXCR1 receptor. Receptors S1P 3, 4 and LPA 1 respectively formed constitutive heterodimers with CXCR1. LPA treatment reduced the amount of LPA 1/CXCR1 heterodimer. Therefore, profiles of S1P and LPA receptors differ between neutrophils of patients with pneumonia and control subjects, with consequences for neutrophil function.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2005 American Thoracic Society. 		  ATS Best of the Web