The critical role of hematopoietic cells in lipopolysaccharide-induced airway inflammation.
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.
Hollingsworth
John W
JW
Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University Medical Center, Box 3221, Durham, NC 27710, USA. holli017@mc.duke.edu
Chen
Benny J
BJ
Brass
David M
DM
Berman
Katie
K
Gunn
M Dee
MD
Cook
Donald N
DN
Schwartz
David A
DA
D000280:Administration, Inhalation; D019264:Adoptive Transfer; D000403:Airway Resistance / Q000276:immunology; D000818:Animals; D046528:Chimerism; D004926:Escherichia coli / Q000276:immunology*; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D018655:Lymphocyte Count; D016676:Macrophages, Alveolar / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000276:immunology*; D009195:Peroxidase / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000276:immunology*; D011650:Pulmonary Alveoli / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000502:physiology*
D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D009195:Peroxidase