Pulmonary stromal-derived factor-1 expression and effect on neutrophil recruitment during acute lung injury.
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.
Petty
Joseph M
JM
Department of Medicine, University of Vermont College of Medicine, 149 Beaumont Avenue, Burlington, VT 05405, USA.
Sueblinvong
Viranuj
V
Lenox
Christopher C
CC
Jones
Christine C
CC
Cosgrove
Gregory P
GP
Cool
Carlyne D
CD
Rai
Pradeep R
PR
Brown
Kevin K
KK
Weiss
Daniel J
DJ
Poynter
Matthew E
ME
Suratt
Benjamin T
BT
D000818:Animals; D002462:Cell Membrane / Q000276:immunology; D002465:Cell Movement; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004848:Epithelium / Q000737:chemistry / Q000276:immunology; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000032:analysis; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000276:immunology*
C515255:CXCL12 protein, human; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C515256:Cxcl12 protein, mouse; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D019718:Receptors, CXCR4