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This information is current as Recruitment during Acute Lung Injury Expression and Effect on Neutrophil Pulmonary Stromal-Derived Factor-1 Matthew E. Poynter and Benjamin T. Suratt Cool, Pradeep R. Rai, Kevin K. Brown, Daniel J. Weiss, Lenox, Christine C. Jones, Gregory P. Cosgrove, Carlyne D. Joseph M. Petty, Viranuj Sueblinvong, Christopher C. http://www.jimmunol.org/content/178/12/8148 doi: 10.4049/jimmunol.178.12.8148 2007;
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2019 http://www.jimmunol.org/ Downloaded from 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. Suratt2 * The severe and protracted in?ammation 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 inves- tigated 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 signi?cantly 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 in?ammatory response to the initiation of tissue repair. The Journal of Immunology, 2007, 178: 8148C8157. A cute lung injury (ALI)3 is de?ned in part by persistent, uncontrolled pulmonary in?ammation that occurs in re- sponse to a variety of insults, including pneumonia, sep- sis, and trauma (1). Hence, pulmonary recruitment of neutrophils appears to be a central factor in both the syndrome'