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) All Versions of this Article: 290/4/L738    most recent 00280.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend 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 Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Fan, J. Articles by Wilson, M. A. Search for Related Content PubMed PubMed Citation Articles by Fan, J. Articles by Wilson, M. A.

Hemorrhagic shock-activated neutrophils augment TLR4 signaling-induced TLR2 upregulation in alveolar macrophages: role in hemorrhage-primed lung inflammation

¹Department of Surgery, School of Medicine, University of Pittsburgh, and ²Surgical Research, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania

Submitted 29 June 2005 ; accepted in final form 1 November 2005

Hemorrhagic shock renders patients susceptible to the development of acute lung injury in response to a second inflammatory stimulus by as yet unclear mechanisms. We investigated the role of neutrophils (PMN) in alveolar macrophage (AM) priming, specifically, the role in mediating Toll-like receptor (TLR)4 and TLR2 cross talk in AM. Using a mouse model of hemorrhagic shock followed by intratracheal administration of LPS, we explored a novel function of shock-activated PMN in the mechanism of TLR2 upregulation induced by LPS-TLR4 signaling in AM. We showed that antecedent hemorrhagic shock enhanced LPS-induced TLR2 upregulation in AM. In neutropenic mice subjected to shock, the LPS-induced TLR2 expression was significantly reduced, and the response was restored upon repletion with PMN obtained from shock-resuscitated mice but not by PMN from sham-operated mice. These findings were recapitulated in mouse AM cocultured with PMN. The enhanced TLR2 upregulation in AM augmented the expression of macrophage inflammatory protein-2, TNF-, and macrophage migration inhibitory factor in the AM in response to sequential challenges of LPS and peptidoglycan, a prototypical TLR2 ligand, which physiologically associated with amplified AM-induced PMN migration into air pouch and lung alveoli. Thus TLR2 expression in AM, signaled by TLR4 and regulated by shock-activated PMN, is an important positive-feedback mechanism responsible for shock-primed PMN infiltration into the lung after primary PMN sequestration.

acute lung injury; lipopolysaccharide; innate immunity; peptidoglycan; Toll-like receptor

This article has been cited by other articles:

				S. Spiller, G. Elson, R. Ferstl, S. Dreher, T. Mueller, M. Freudenberg, B. Daubeuf, H. Wagner, and C. J. Kirschning TLR4-induced IFN-{gamma} production increases TLR2 sensitivity and drives Gram-negative sepsis in mice J. Exp. Med., August 4, 2008; 205(8): 1747 - 1754. [Abstract] [Full Text] [PDF]