help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

Published ahead of print on June 21, 2007, doi:10.1165/rcmb.2007-0153OC
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2007-0153OCv1
37/5/562    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 Serezani, C. H.
Right arrow Articles by Peters-Golden, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Serezani, C. H.
Right arrow Articles by Peters-Golden, M.
American Journal of Respiratory Cell and Molecular Biology. Vol. 37, pp. 562-570, 2007
© 2007 American Thoracic Society
DOI: 10.1165/rcmb.2007-0153OC

Prostaglandin E2 Suppresses Bacterial Killing in Alveolar Macrophages by Inhibiting NADPH Oxidase

Carlos H. Serezani1, Jooho Chung1, Megan N. Ballinger1, Bethany B. Moore1, David M. Aronoff2 and Marc Peters-Golden1

1 Division of Pulmonary and Critical Care Medicine; and 2 Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Health Systems, Ann Arbor, Michigan

Correspondence and requests for reprints should be addressed to Marc Peters-Golden, M.D., 6301 MSRB III, Box 0642; 1150 W. Medical Center Drive, University of Michigan Health System, Ann Arbor, MI 48109-0642. E-mail: petersm{at}umich.edu

Prostaglandin E2 (PGE2) is a potent lipid mediator that effects changes in cell functions through ligation of four distinct G protein–coupled E prostanoid (EP) receptors (EP1–EP4). PGE2 inhibits bacterial killing and reactive oxygen intermediate (ROI) production by alveolar macrophages (AMs), although little is known about the operative molecular mechanisms. The aims of this study were to evaluate the molecular mechanisms and the specific EP receptors through which PGE2 inhibits killing of Klebsiella pneumoniae by AMs. The treatment of AMs with PGE2 suppressed the killing of K. pneumoniae, and this effect was blocked by an adenylyl cyclase inhibitor and mimicked by agonists for the stimulatory G protein (Gs)-coupled EP2 and EP4 receptors. Conversely, microbicidal activity was augmented by pretreatment with the cyclooxygenase inhibitor, indomethacin, and antagonists of EP2 and EP4. Similar results were found when ROI production was examined. PGE2 inhibition of killing and ROI generation was associated with its activation of the cAMP effectors, protein kinase A and exchange protein directly activated by cAMP-1, as well as attenuation of the phosphorylation and translocation of the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase component, p47phox, to the phagosomal membrane. We conclude that PGE2 suppresses the microbicidal activity of AMs through the Gs-coupled EP2/EP4 receptors, with increased cAMP inhibiting the assembly and activation of p47phox.

Key Words: bacterial killing • lipid mediators • macrophage • phagosome • prostaglandin E2 • NADPH


CLINICAL RELEVANCE

This study identifies an important role of prostaglandin E2 acting through E prostanoid (EP) 2 and EP4 receptors to limit alveolar macrophage microbicidal activity, provides new insights into the regulation of innate immune cells, and suggests potential strategies for immunostimulant therapeutics.

 






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2007 American Thoracic Society.
  ATS Best of the Web