The Journal of Experimental Medicine
Avanti Polar Lipids, Inc.
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online
doi:10.1084/jem.20070494
The Journal of Experimental Medicine, Vol. 204, No. 8, 1901-1909
The Rockefeller University Press, 0022-1007 $30.00
© Benarafa et al.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 2781K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Benarafa, C.
Right arrow Articles by Remold-O'Donnell, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Benarafa, C.
Right arrow Articles by Remold-O'Donnell, E.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

ARTICLE

 The neutrophil serine protease inhibitor serpinb1 preserves lung defense functions in Pseudomonas aeruginosa infection

Charaf Benarafa1,2, Gregory P. Priebe3,4, and Eileen Remold-O'Donnell1,2

1 CBR Institute for Biomedical Research and 2 Department of Pediatrics, Harvard Medical School, Boston, MA 02115
3 Channing Laboratory, Brigham and Women's Hospital and 4 Department of Anesthesia (Critical Care Medicine) and Department of Medicine (Infectious Diseases), Children's Hospital Boston, Boston, MA 02115

CORRESPONDENCE Charaf Benarafa: benarafa{at}cbr.med.harvard.edu

Neutrophil serine proteases (NSPs; elastase, cathepsin G, and proteinase-3) directly kill invading microbes. However, excess NSPs in the lungs play a central role in the pathology of inflammatory pulmonary disease. We show that serpinb1, an efficient inhibitor of the three NSPs, preserves cell and molecular components responsible for host defense against Pseudomonas aeruginosa. On infection, wild-type (WT) and serpinb1-deficient mice mount similar early responses, including robust production of cytokines and chemokines, recruitment of neutrophils, and initial containment of bacteria. However, serpinb1–/– mice have considerably increased mortality relative to WT mice in association with late-onset failed bacterial clearance. We found that serpinb1-deficient neutrophils recruited to the lungs have an intrinsic defect in survival accompanied by release of neutrophil protease activity, sustained inflammatory cytokine production, and proteolysis of the collectin surfactant protein–D (SP-D). Coadministration of recombinant SERPINB1 with the P. aeruginosa inoculum normalized bacterial clearance in serpinb1–/– mice. Thus, regulation of pulmonary innate immunity by serpinb1 is nonredundant and is required to protect two key components, the neutrophil and SP-D, from NSP damage during the host response to infection.

Abbreviations used: AnV, annexin V; BAL, bronchoalveolar; CG, cathepsin G; ES, embryonic stem; FSC, forward scatter; hpf, high power field; KC, keratino cyte-derived chemokine; MPO, myeloperoxidase; NE, neutrophil elastase; NSP, neutrophil serine protease; PI, propidium iodide; rrSP-D, recombinant rat SP-D; SP-D, surfactant protein–D; TSA, tryptic soy agar.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS