| First Author | Standiford LR | Year | 2012 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 302 |
| Issue | 5 | Pages | L447-54 |
| PubMed ID | 22160309 | Mgi Jnum | J:183448 |
| Mgi Id | MGI:5318675 | Doi | 10.1152/ajplung.00415.2010 |
| Citation | Standiford LR, et al. (2012) TLR4-dependent GM-CSF protects against lung injury in Gram-negative bacterial pneumonia. Am J Physiol Lung Cell Mol Physiol 302(5):L447-54 |
| abstractText | Toll-like receptors (TLRs) are required for protective host defense against bacterial pathogens. However, the role of TLRs in regulating lung injury during Gram-negative bacterial pneumonia has not been thoroughly investigated. In this study, experiments were performed to evaluate the role of TLR4 in pulmonary responses against Klebsiella pneumoniae (Kp). Compared with wild-type (WT) (Balb/c) mice, mice with defective TLR4 signaling (TLR4(lps-d) mice) had substantially higher lung bacterial colony-forming units after intratracheal challenge with Kp, which was associated with considerably greater lung permeability and lung cell death. Reduced expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA and protein was noted in lungs and bronchoalveolar lavage fluid of TLR4 mutant mice postintratracheal Kp compared with WT mice, and primary alveolar epithelial cells (AEC) harvested from TLR4(lps-d) mice produced significantly less GM-CSF in vitro in response to heat-killed Kp compared with WT AEC. TLR4(lps-d) AEC underwent significantly more apoptosis in response to heat-killed Kp in vitro, and treatment with GM-CSF protected these cells from apoptosis in response to Kp. Finally, intratracheal administration of GM-CSF in TLR4(lps-d) mice significantly decreased albumin leak, lung cell apoptosis, and bacteremia in Kp-infected mice. Based on these observations, we conclude that TLR4 plays a protective role on lung epithelium during Gram-negative bacterial pneumonia, an effect that is partially mediated by GM-CSF. |
