HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fillon, S. Articles by Tuomanen, E. I. Search for Related Content PubMed PubMed Citation Articles by Fillon, S. Articles by Tuomanen, E. I.

Platelet-Activating Factor Receptor and Innate Immunity: Uptake of Gram-Positive Bacterial Cell Wall into Host Cells and Cell-Specific Pathophysiology

Sophie Fillon^1,*, Konstantinos Soulis^1,*, Surender Rajasekaran^1,, Heather Benedict-Hamilton, Jana N. Radin^*, Carlos J. Orihuela^*, Karim C. El Kasmi^*, Gopal Murti, Deepak Kaushal, M. Waleed Gaber^¶, Joerg R. Weber^||, Peter J. Murray^* and Elaine I. Tuomanen^2,*

^* Department of Infectious Diseases, Division of Critical Care Medicine, Department of Molecular Biotechnology, and Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children’s Research Hospital, Memphis TN 38105; ^¶ Department of Biomedical Engineering, University of Tennessee, Memphis, TN 38163; and ^|| Department of Neurology, Charite-Universitaetsmedizin, Berlin, Germany

The current model of innate immune recognition of Gram-positive bacteria suggests that the bacterial cell wall interacts with host recognition proteins such as TLRs and Nod proteins. We describe an additional recognition system mediated by the platelet-activating factor receptor (PAFr) and directed to the pathogen-associated molecular pattern phosphorylcholine that results in the uptake of bacterial components into host cells. Intravascular choline-containing cell walls bound to endothelial cells and caused rapid lethality in wild-type, Tlr2^–/–, and Nod2^–/– mice but not in Pafr^–/– mice. The cell wall exited the vasculature into the heart and brain, accumulating within endothelial cells, cardiomyocytes, and neurons in a PAFr-dependent way. Physiological consequences of the cell wall/PAFr interaction were cell specific, being noninflammatory in endothelial cells and neurons but causing a rapid loss of cardiomyocyte contractility that contributed to death. Thus, PAFr shepherds phosphorylcholine-containing bacterial components such as the cell wall into host cells from where the response ranges from quiescence to severe pathophysiology.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ S.F., K.S., and S.R. contributed equally to this work.

² Address correspondence and reprint requests to Dr. Elaine I. Tuomanen, Department of Infectious Diseases, St. Jude Children’s Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105. E-mail address: elaine.tuomanen{at}stjude.org

³ Abbreviations used in this paper: PAMP, pathogen-associated molecular patterns; CDP, cytidine diphosphate; DAPI, 4',6-diamidino-3-phenylindole; GPCR, G protein-coupled receptor; LVdevP, left ventricular developed pressure; PAF, platelet-activating factor; PAFr, PAF receptor; PLC, phospholipase C; RT, room temperature; TMB, tetramethylbenzidine.

This article has been cited by other articles:

				R. A. Frost and C. H. Lang Regulation of muscle growth by pathogen-associated molecules J Anim Sci, April 1, 2008; 86(14_suppl): E84 - E93. [Abstract] [Full Text] [PDF]

				C. J. Kuckleburg, S. F. Elswaifi, T. J. Inzana, and C. J. Czuprynski Expression of Phosphorylcholine by Histophilus somni Induces Bovine Platelet Aggregation Infect. Immun., February 1, 2007; 75(2): 1045 - 1049. [Abstract] [Full Text] [PDF]