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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Petty, J. M. Articles by Suratt, B. T. Search for Related Content PubMed PubMed Citation Articles by Petty, J. M. Articles by Suratt, B. T.

Pulmonary Stromal-Derived Factor-1 Expression and Effect on Neutrophil Recruitment during Acute Lung Injury¹

Joseph M. Petty^*, Viranuj Sueblinvong^*, Christopher C. Lenox^*, Christine C. Jones^*, Gregory P. Cosgrove, Carlyne D. Cool, Pradeep R. Rai, Kevin K. Brown, Daniel J. Weiss^*, Matthew E. Poynter^* and Benjamin T. Suratt^2,*

^* Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05405; and Department of Medicine and Department of Pathology, National Jewish Medical and Research Center, Denver, CO 80206

The severe and protracted inflammation that characterizes acute lung injury (ALI) is driven by the ongoing recruitment of neutrophils to the lung. Although much of the cytokine signaling responsible for the initial phase of ALI has been elaborated, relatively little is known about the mechanisms governing the recruitment of neutrophils from the bone marrow to the lung in the later period of this disease. Given its previously described chemoattractant effects on marrow neutrophils, we investigated whether stromal-derived factor-1 (SDF-1) (CXCL12) might participate in this later phase of recruitment. Using immunohistochemistry to examine both banked human lung specimens from patients with ALI and lungs from mice with LPS-induced pneumonitis, we found that pulmonary SDF-1 expression increases during ALI. We further determined that both lung SDF-1 protein expression and mRNA expression rise in a delayed but sustained pattern in this mouse model and that the major source of the increase in expression appears to be the lung epithelium. Lastly, we found that expression of the SDF-1 receptor CXCR4 rises in a similar temporal pattern on neutrophils in both the blood and airspace of LPS-injured mice and that Ab-mediated SDF-1 blockade significantly attenuates late but not early pulmonary neutrophilia in this model. These results implicate SDF-1 in neutrophil recruitment to the lung in the later period of acute lung injury and suggest a novel role for this cytokine in coordinating the transition from the inflammatory response to the initiation of tissue repair.

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 This work was supported by National Institutes of Health Grants K08 HL04499 and 1R01 HL084200.

² Address correspondence and reprint requests to Dr. Benjamin T. Suratt, University of Vermont College of Medicine, 149 Beaumont Avenue, HSRF 230, Burlington, VT 05405. E-mail address: benjamin.suratt{at}uvm.edu

³ Abbreviations used in this paper: ALI, acute lung injury; BAL, bronchoalveolar lavage; IHC, immunohistochemistry; SDF-1, stromal-derived factor-1.

This article has been cited by other articles:

				M. Makam, D. Diaz, J. Laval, Y. Gernez, C. K. Conrad, C. E. Dunn, Z. A. Davies, R. B. Moss, L. A. Herzenberg, L. A. Herzenberg, et al. Activation of critical, host-induced, metabolic and stress pathways marks neutrophil entry into cystic fibrosis lungs PNAS, April 7, 2009; 106(14): 5779 - 5783. [Abstract] [Full Text] [PDF]

				P. L. Wagner, E. Hyjek, M. F. Vazquez, D. Meherally, Y. F. Liu, P. A. Chadwick, T. Rengifo, G. L. Sica, J. L. Port, P. C. Lee, et al. CXCL12 and CXCR4 in adenocarcinoma of the lung: association with metastasis and survival. J. Thorac. Cardiovasc. Surg., March 1, 2009; 137(3): 615 - 621. [Abstract] [Full Text] [PDF]

				Z. Dubeykovskaya, A. Dubeykovskiy, J. Solal-Cohen, and T. C. Wang Secreted Trefoil Factor 2 Activates the CXCR4 Receptor in Epithelial and Lymphocytic Cancer Cell Lines J. Biol. Chem., February 6, 2009; 284(6): 3650 - 3662. [Abstract] [Full Text] [PDF]

				Z. Bai, H. Hayasaka, M. Kobayashi, W. Li, Z. Guo, M. H. Jang, A. Kondo, B.-i. Choi, Y. Iwakura, and M. Miyasaka CXC Chemokine Ligand 12 Promotes CCR7-Dependent Naive T Cell Trafficking to Lymph Nodes and Peyer's Patches J. Immunol., February 1, 2009; 182(3): 1287 - 1295. [Abstract] [Full Text] [PDF]

				J. M. Petty, C. C. Lenox, D. J. Weiss, M. E. Poynter, and B. T. Suratt Crosstalk between CXCR4/Stromal Derived Factor-1 and VLA-4/VCAM-1 Pathways Regulates Neutrophil Retention in the Bone Marrow J. Immunol., January 1, 2009; 182(1): 604 - 612. [Abstract] [Full Text] [PDF]

				N. J. Serkova, Z. Van Rheen, M. Tobias, J. E. Pitzer, J. E. Wilkinson, and K. A. Stringer Utility of magnetic resonance imaging and nuclear magnetic resonance-based metabolomics for quantification of inflammatory lung injury Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L152 - L161. [Abstract] [Full Text] [PDF]

				X. Su, M. Johansen, M. R. Looney, E. J. Brown, and M. A. Matthay CD47 Deficiency Protects Mice from Lipopolysaccharide-Induced Acute Lung Injury and Escherichia coli Pneumonia J. Immunol., May 15, 2008; 180(10): 6947 - 6953. [Abstract] [Full Text] [PDF]