| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Medicine, VA Puget Sound Health Care System and the Division of Pulmonary and Critical Care Medicine, Seattle, WA, USA; Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Pittsburgh, PA, USA
2 Department of Medicine, VA Puget Sound Health Care System and the Division of Pulmonary and Critical Care Medicine, Seattle, WA, USA
3 Department of Thoracic Medicine II, Chang Gung Memorial Hospital, Taipei, Taiwan
* To whom correspondence should be addressed. E-mail: leejs3{at}upmc.edu.
We examined the role of TLR-4 in modifying the lung inflammatory response and its effects on the bacterial recovery from the lungs following inhaled E. coli using two different strains of TLR-4 mutant mice that are hyporesponsive to LPS. The C57Bl/10ScN(tlr4lps-del) mice containing a deletion mutation in the TLR-4 gene showed lower pro-inflammatory cytokine levels, lower lung MPO activity, and less parenchymal and peribronchial inflammation when compared to the C57Bl/10ScSn mice, a related TLR-4 wildtype substrain. However, the C57Bl/10ScN(tlr4lps-del) mutant showed lower bacterial recovery in the lungs following inhaled E. coli associated with a rapid but transient increase in airspace neutrophil counts at 6 h. In comparison, the C3H/HeJ(tlr4Lps-d) mutant mice containing a Pro712His substitution in TLR-4 demonstrated lower pro-inflammatory cytokine levels, lower lung MPO activity, and lower neutrophil accumulation in the airspaces but showed no differences in the bacterial burden of inhaled E. coli at 6 h, when compared with the TLR-4 wildtype C3H/HeSnJ mice. Thus, two different TLR-4 mutants showed attenuated inflammatory responses in the lungs, but the reduced inflammatory responses were not consistently associated with either improved or impaired bacterial elimination from the lungs. Our findings indicate that the inflammatory response to inhaled E. coli is TLR-4 dependent, but bacterial elimination depends on other factors in addition to TLR-4.
This article has been cited by other articles:
|
|
 |
|
  R. A. Bem, A. W. Farnand, V. Wong, A. Koski, M. E. Rosenfeld, N. van Rooijen, C. W. Frevert, T. R. Martin, and G. Matute-Bello Depletion of resident alveolar macrophages does not prevent Fas-mediated lung injury in mice Am J Physiol Lung Cell Mol Physiol, August 1, 2008; 295(2): L314 - L325. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. G. Clement, S. E. Evans, C. M. Evans, D. Hawke, R. Kobayashi, P. R. Reynolds, S. J. Moghaddam, B. L. Scott, E. Melicoff, R. Adachi, et al. Stimulation of Lung Innate Immunity Protects against Lethal Pneumococcal Pneumonia in Mice Am. J. Respir. Crit. Care Med., June 15, 2008; 177(12): 1322 - 1330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. S. Tang, M. Mura, R. Seth, and M. Liu Acute lung injury and cell death: how many ways can cells die? Am J Physiol Lung Cell Mol Physiol, April 1, 2008; 294(4): L632 - L641. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Chaudhuri, M. K. B. Whyte, and I. Sabroe Reducing the Toll of Inflammatory Lung Disease Chest, May 1, 2007; 131(5): 1550 - 1556. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Elson, I. Dunn-Siegrist, B. Daubeuf, and J. Pugin Contribution of Toll-like receptors to the innate immune response to Gram-negative and Gram-positive bacteria Blood, February 15, 2007; 109(4): 1574 - 1583. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Skerrett, C. B. Wilson, H. D. Liggitt, and A. M. Hajjar Redundant Toll-like receptor signaling in the pulmonary host response to Pseudomonas aeruginosa Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L312 - L322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. R. Martin and C. W. Frevert Innate Immunity in the Lungs Proceedings of the ATS, December 1, 2005; 2(5): 403 - 411. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
