Document Detail


Lung-marginated monocytes modulate pulmonary microvascular injury during early endotoxemia.
MedLine Citation:
PMID:  16081546     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: The role of monocytes in acute endotoxemia has been ascribed to systemic release of mediators within the central circulation. Little is known about the potential role of "marginated" monocytes in regulating microvascular inflammatory signaling.
OBJECTIVES: To investigate whether lung-marginated monocytes can locally activate pulmonary endothelial cells through cell contact-dependent interactions in early endotoxemia.
METHODS: Mice were challenged with LPS to produce acute endotoxemia and pulmonary vascular injury. Adoptive transfer of ex vivo LPS-stimulated donor leukocytes to recipient mice was also performed to evaluate cell-associated inflammatory signaling between monocytes and endothelial cells within the lung. Cell suspensions from excised lungs were analyzed by flow cytometry for expression of tumor necrosis factor alpha (TNF-alpha) on monocytes and cell adhesion molecules on endothelial cells.
RESULTS: Substantial numbers of monocytes rapidly marginated to the lungs after endotoxin challenge in mice, and lung-marginated monocytes expressed significantly higher levels of membrane TNF than circulating monocytes, due to higher TNF production by the marginated cells. Injection of activated wild-type donor leukocytes to wild-type or TNF receptor double knockout recipients demonstrated that lung-marginated monocytes can induce TNF-dependent upregulation of adhesion molecules on pulmonary endothelial cells. Injection of activated donor leukocytes from TNF knock-in mice that express uncleavable mutant membrane TNF also induced adhesion molecule upregulation in wild-type recipients without a systemic soluble TNF release.
CONCLUSIONS: These results reveal a previously unacknowledged role for lung-marginated monocytes in early endotoxemia, exerting local, cell-associated TNF signaling within the pulmonary microcirculation, contributing to the evolution of pulmonary vascular injury.
Authors:
Kieran P O'Dea; Arnold J Young; Hirotoshi Yamamoto; James L Robotham; Fionula M Brennan; Masao Takata
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-08-04
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  172     ISSN:  1073-449X     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-10-26     Completed Date:  2006-01-19     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1119-27     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Adhesion Molecules / metabolism*
Cell Communication / physiology
Disease Models, Animal
Endotoxemia / chemically induced,  metabolism*,  pathology
Epithelial Cells / physiology
Lipopolysaccharides
Lung / metabolism*,  pathology
Male
Membrane Proteins / metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Monocytes / physiology*
Tumor Necrosis Factor-alpha / metabolism*
Grant Support
ID/Acronym/Agency:
G0000101//Medical Research Council; //Wellcome Trust
Chemical
Reg. No./Substance:
0/Cell Adhesion Molecules; 0/Lipopolysaccharides; 0/Membrane Proteins; 0/Tumor Necrosis Factor-alpha; 0/lipopolysaccharide, Escherichia coli 0111 B4

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