Published ahead of print on October 17, 2003, doi:10.1165/rcmb.2003-0253OC
Am. J. Respir. Cell Mol. Biol., Volume 30, Number 4, April 2004, 576-584
A more recent version of this article appeared on April 1, 2004
Submitted on July 7, 2003
Revised on October 15, 2003
Deficiency in neutrophil elastase does not impair neutrophil recruitment to inflamed sites
Tim O Hirche1, Jefferey J Atkinson1, Scott Bahr1, and Abderrazzaq Belaaouaj2*
1 Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA,
2 Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, Missouri, USA
* To whom correspondence should be addressed. E-mail: belaaouaja{at}msnotes.wustl.edu.
To reach the sites of inflammation, neutrophils traverse the endothelium, its underlying basement membrane, and other barriers depending on the localization of the insulting agent. Whether neutrophil elastase (NE) plays a role in neutrophil recruitment to inflamed sites is still debatable. By exploiting mice deficient in NE (NE-/-), we sought to address this dilemma. We recruited neutrophils to the lungs or the peritoneum of wild type (WT) or NE-/- mice by intranasal or intraperitoneal challenge with Pseudomonas aeruginosa or its lipopolysaccharide. At designated times post-inoculation (0, 4, 24 and 48 h), groups of mice were sacrificed to assess changes in leukocyte counts and inflammatory responses. NE-/- and WT mice had normal circulating leukocyte numbers including neutrophils and changes in the hemograms in the setting of acute inflammation were indistinguishable. Analyses of lung tissues or fluids from the lungs and peritoneum found that regardless of the inflammatory model, the leukocyte counts including neutrophils and the inflammatory response were similar in NE-/- and WT mice at all time points. In vitro, neutrophils isolated from the lungs or the peritoneum of NE-/- and WT mice had comparable chemotactic and respiratory-burst functions and migrated normally through Matrigel® in response to various stimuli. Interestingly, preincubation of human peripheral blood neutrophils with NE physiologic inhibitors did not alter the migration of the cells through Matrigel®. In sum, our findings present the first in vivo description that the absence of NE does not impair neutrophil recruitment to inflamed sites and that NE is not required for basement membrane transmigration of neutrophils.
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