This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 200407-953OCv1 171/8/806    most recent Alert me when this article is cited Alert me if a correction is posted 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 Hollingsworth, J. W. Articles by Schwartz, D. A. Search for Related Content PubMed PubMed Citation Articles by Hollingsworth, J. W. Articles by Schwartz, D. A.

The Critical Role of Hematopoietic Cells in Lipopolysaccharide-induced Airway Inflammation

Divisions of Pulmonary, Allergy, and Critical Care Medicine, Cellular Therapy, and Cardiology, Duke University Medical Center; Veterans Administration Medical Center, Durham, North Carolina

Correspondence and requests for reprints should be addressed to John W. Hollingsworth, M.D., Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University Medical Center, Box 3221, Durham, NC 27710. E-mail: holli017{at}mc.duke.edu

Rapid and selective recruitment of neutrophils into the airspace in response to LPS facilitates the clearance of bacterial pathogens. However, neutrophil infiltration can also participate in the development and progression of environmental airway disease. Previous data have revealed that Toll-like receptor 4 (tlr4) is required for neutrophil recruitment to the lung after either inhaled or systemically administrated LPS from Escherichia coli. Although many cell types express tlr4, endothelial cell expression of tlr4 is specifically required to sequester neutrophils in the lung in response to systemic endotoxin. To identify the cell types requiring trl4 expression for neutrophil recruitment after inhaled LPS, we generated chimeric mice separately expressing tlr4 on either hematopoietic cells or on structural lung cells. Neutrophil recruitment into the airspace was completely restored in tlr4-deficient mice receiving wild-type bone marrow. By contrast, wild-type animals receiving tlr4-deficient marrow had dramatically reduced neutrophil recruitment. Moreover, adoptive transfer of wild-type alveolar macrophages also restored the ability of tlr4-deficient recipient mice to recruit neutrophils to the lung. These data demonstrate the critical role of hematopoietic cells and alveolar macrophages in initiating LPS-induced neutrophil recruitment from the vascular space to the airspace.

Key Words: innate immunity • lipopolysaccharide • macrophage • neutrophil • toll-like receptor

This article has been cited by other articles:

				L. C. Parker, E. C. Prestwich, J. R. Ward, E. Smythe, A. Berry, M. Triantafilou, K. Triantafilou, and I. Sabroe A Phosphatidylserine Species Inhibits a Range of TLR- but Not IL-1{beta}-Induced Inflammatory Responses by Disruption of Membrane Microdomains J. Immunol., October 15, 2008; 181(8): 5606 - 5617. [Abstract] [Full Text] [PDF]

				X. Zhao, J. W. Zmijewski, E. Lorne, G. Liu, Y.-J. Park, Y. Tsuruta, and E. Abraham Activation of AMPK attenuates neutrophil proinflammatory activity and decreases the severity of acute lung injury Am J Physiol Lung Cell Mol Physiol, September 1, 2008; 295(3): L497 - L504. [Abstract] [Full Text] [PDF]

				S. Hadina, J. P. Weiss, P. B. McCray Jr., K. Kulhankova, and P. S. Thorne MD-2-Dependent Pulmonary Immune Responses to Inhaled Lipooligosaccharides: Effect of Acylation State Am. J. Respir. Cell Mol. Biol., June 1, 2008; 38(6): 647 - 654. [Abstract] [Full Text] [PDF]

				I Sabroe, L C Parker, P M A Calverley, S K Dower, and M K B Whyte Pathological networking: a new approach to understanding COPD Postgrad. Med. J., May 1, 2008; 84(991): 259 - 264. [Abstract] [Full Text] [PDF]

				K. P. Mollen, R. M. Levy, J. M. Prince, R. A. Hoffman, M. J. Scott, D. J. Kaczorowski, R. Vallabhaneni, Y. Vodovotz, and T. R. Billiar Systemic inflammation and end organ damage following trauma involves functional TLR4 signaling in both bone marrow-derived cells and parenchymal cells J. Leukoc. Biol., January 1, 2008; 83(1): 80 - 88. [Abstract] [Full Text] [PDF]

				I. Sabroe, L. C. Parker, S. K. Dower, and M. K. B. Whyte Practical and Conceptual Models of Chronic Obstructive Pulmonary Disease Proceedings of the ATS, December 1, 2007; 4(8): 606 - 610. [Abstract] [Full Text] [PDF]

				I. Sabroe, L. C Parker, P. M A Calverley, S. K Dower, and M. K B Whyte Pathological networking: a new approach to understanding COPD Thorax, August 1, 2007; 62(8): 733 - 738. [Abstract] [Full Text] [PDF]

				J. W. Hollingsworth, Z. Li, D. M. Brass, S. Garantziotis, S. H. Timberlake, A. Kim, I. Hossain, R. C. Savani, and D. A. Schwartz CD44 Regulates Macrophage Recruitment to the Lung in Lipopolysaccharide-Induced Airway Disease Am. J. Respir. Cell Mol. Biol., August 1, 2007; 37(2): 248 - 253. [Abstract] [Full Text] [PDF]

				J. W. Hollingsworth, S. R. Kleeberger, and W. M. Foster Ozone and Pulmonary Innate Immunity Proceedings of the ATS, July 1, 2007; 4(3): 240 - 246. [Abstract] [Full Text] [PDF]

				D. M. Brass, J. W. Hollingsworth, E. McElvania-Tekippe, S. Garantziotis, I. Hossain, and D. A. Schwartz CD14 is an essential mediator of LPS-induced airway disease Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L77 - L83. [Abstract] [Full Text] [PDF]

				N. Chaudhuri, M. K. B. Whyte, and I. Sabroe Reducing the Toll of Inflammatory Lung Disease Chest, May 1, 2007; 131(5): 1550 - 1556. [Abstract] [Full Text] [PDF]

				I. Sabroe, L. C. Parker, D. H. Dockrell, D. E. Davies, S. K. Dower, and M. K. B. Whyte Targeting the Networks that Underpin Contiguous Immunity in Asthma and Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., February 15, 2007; 175(4): 306 - 311. [Abstract] [Full Text] [PDF]

				G. E. Morris, L. C. Parker, J. R. Ward, E. C. Jones, M. K. B. Whyte, C. E. Brightling, P. Bradding, S. K. Dower, and I. Sabroe Cooperative molecular and cellular networks regulate Toll-like receptor-dependent inflammatory responses FASEB J, October 1, 2006; 20(12): 2153 - 2155. [Abstract] [Full Text] [PDF]

				E. Abraham, J. A. Nick, T. Azam, S. H. Kim, J.-P. Mira, D. Svetkauskaite, Q. He, M. Zamora, J. Murphy, J. S. Park, et al. Peripheral blood neutrophil activation patterns are associated with pulmonary inflammatory responses to lipopolysaccharide in humans. J. Immunol., June 15, 2006; 176(12): 7753 - 7760. [Abstract] [Full Text] [PDF]

				A. E. Medvedev, I. Sabroe, J. D. Hasday, and S. N. Vogel Invited review: Tolerance to microbial TLR ligands: molecular mechanisms and relevance to disease Innate Immunity, June 1, 2006; 12(3): 133 - 150. [Abstract] [PDF]

				J. W. Hollingsworth, G. S. Whitehead, K. L. Lin, H. Nakano, M. D. Gunn, D. A. Schwartz, and D. N. Cook TLR4 Signaling Attenuates Ongoing Allergic Inflammation J. Immunol., May 15, 2006; 176(10): 5856 - 5862. [Abstract] [Full Text] [PDF]

				S. E. Wenzel and R. Covar Update in asthma 2005. Am. J. Respir. Crit. Care Med., April 1, 2006; 173(7): 698 - 706. [Full Text] [PDF]

				J. W. Chien, L. P. Zhao, J. A. Hansen, W. H. Fan, T. Parimon, and J. G. Clark Genetic variation in bactericidal/permeability-increasing protein influences the risk of developing rapid airflow decline after hematopoietic cell transplantation Blood, March 1, 2006; 107(5): 2200 - 2207. [Abstract] [Full Text] [PDF]

				A. M. Hajjar, H. Harowicz, H. D. Liggitt, P. J. Fink, C. B. Wilson, and S. J. Skerrett An Essential Role for Non-Bone Marrow-Derived Cells in Control of Pseudomonas aeruginosa Pneumonia Am. J. Respir. Cell Mol. Biol., November 1, 2005; 33(5): 470 - 475. [Abstract] [Full Text] [PDF]