Document Detail

Stimulation of lung innate immunity protects against lethal pneumococcal pneumonia in mice.
MedLine Citation:
PMID:  18388354     Owner:  NLM     Status:  MEDLINE    
RATIONALE: The lungs are a common site of serious infection in both healthy and immunocompromised subjects, and the most likely route of delivery of a bioterror agent. Since the airway epithelium shows great structural plasticity in response to inflammatory stimuli, we hypothesized it might also show functional plasticity.
OBJECTIVES: To test the inducibility of lung defenses against bacterial challenge.
METHODS: Mice were treated with an aerosolized lysate of ultraviolet-killed nontypeable (unencapsulated) Haemophilus influenzae (NTHi), then challenged with a lethal dose of live Streptococcus pneumoniae (Spn) delivered by aerosol.
MEASUREMENTS AND MAIN RESULTS: Treatment with the NTHi lysate induced complete protection against challenge with a lethal dose of Spn if treatment preceded challenge by 4 to 24 hours. Lesser levels of protection occurred at shorter (83% at 2 h) and longer (83% at 48-72 h) intervals between treatment and challenge. There was also some protection when treatment was given 2 hours after challenge (survival increased from 14 to 57%), but not 24 hours after challenge. Protection did not depend on recruited neutrophils or resident mast cells and alveolar macrophages. Protection was specific to the airway route of infection, correlated in magnitude and time with rapid bacterial killing within the lungs, and was associated with increases of multiple antimicrobial polypeptides in lung lining fluid.
CONCLUSIONS: We infer that protection derives from stimulation of local innate immune mechanisms, and that activated lung epithelium is the most likely cellular effector of this response. Augmentation of innate antimicrobial defenses of the lungs might have therapeutic value.
Cecilia G Clement; Scott E Evans; Christopher M Evans; David Hawke; Ryuji Kobayashi; Paul R Reynolds; Seyed J Moghaddam; Brenton L Scott; Ernestina Melicoff; Roberto Adachi; Burton F Dickey; Michael J Tuvim
Related Documents :
6486244 - Role of polymorphonuclear leukocytes in silica-induced pulmonary fibrosis.
20937404 - Effect of mometasone furoate (mf)/formoterol fumarate (f) combination (mf/f) on late-ph...
9364 - Factors influencing the immune enhancement of intrapulmonary bactericidal mechanisms.
3148794 - A reversible model of acute lung injury based on ozone exposure.
12421364 - Neuroprotective effects of bcl-2 overexpression in hippocampal cultures: interactions w...
15663184 - Effect of orally administered l-tryptophan on serotonin, melatonin, and the innate immu...
Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-04-03
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  177     ISSN:  1535-4970     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-06-04     Completed Date:  2008-06-13     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1322-30     Citation Subset:  AIM; IM    
Department of Pulmonary Medicine, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009. USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Adjuvants, Immunologic / pharmacology*
Bronchoalveolar Lavage Fluid / immunology
Cell Extracts / administration & dosage,  pharmacology*
Colony Count, Microbial
Dose-Response Relationship, Immunologic
Immunity, Innate*
Immunocompromised Host
Mice, Inbred BALB C
Neutrophil Infiltration
Pneumonia, Pneumococcal / immunology*,  prevention & control*
Respiratory Mucosa / immunology
Survival Analysis
Grant Support
Reg. No./Substance:
0/Adjuvants, Immunologic; 0/Aerosols; 0/Broncho-Vaxom; 0/Cell Extracts

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Idiopathic nonspecific interstitial pneumonia: report of an American Thoracic Society project.
Next Document:  Hepatotoxicity of pyrazinamide: cohort and case-control analyses.