| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
during pulmonary ischemia-reperfusion injury
1 Surgery, University of Virginia, Charlottesville, Virginia, United States
2 Medicine, University of Virginia, Charlottesville, Virginia, United States
* To whom correspondence should be addressed. E-mail: vel8n{at}virginia.edu.
Pulmonary ischemia-reperfusion (IR) injury entails acute activation of alveolar macrophages followed by neutrophil sequestration. Although proinflammatory cytokines and chemokines such as TNF-
and MCP-1 from macrophages are known to modulate acute IR injury, the contribution of alveolar epithelial cells to IR injury and their intercellular interactions with other cell types such as alveolar macrophages and neutrophils remain unclear. In this study we tested the hypothesis that following IR, alveolar macrophage-produced TNF- further induces alveolar epithelial cells to produce key chemokines which could then contribute to subsequent lung injury through the recruitment of neutrophils. Cultured RAW264.7 macrophages and MLE12 alveolar epithelial cells were subjected to acute hypoxia-reoxygenation (H/R) as an in vitro model of pulmonary IR. H/R (3h/1h) significantly induced KC, MCP-1, MIP-2, RANTES and IL-6 (but not TNF-) by MLE12 cells whereas H/R induced TNF-, MCP-1, RANTES, MIP-1 and MIP-2 (but not KC) by RAW264.7 cells. These results were confirmed using primary murine alveolar macrophages and primary alveolar type II cells. Importantly, using macrophage and epithelial co-culture methods, the specific production of TNF- by H/R-exposed RAW264.7 cells significantly induced proinflammatory cytokine/chemokine expression (KC, MCP-1, MIP-2, RANTES and IL-6) by MLE12 cells. Collectively, these results demonstrate that alveolar type II cells, in conjunction with alveolar macrophage-produced TNF-, contribute to the initiation of acute pulmonary IR injury via a proinflammatory cascade. The release of key chemokines, such as KC and MIP-2, by activated type II cells may thus significantly contribute to neutrophil sequestration during IR injury.
This article has been cited by other articles:
|
|
 |
|
  M. Cypel, M. Liu, M. Rubacha, J. C. Yeung, S. Hirayama, M. Anraku, M. Sato, J. Medin, B. L. Davidson, M. de Perrot, et al. Functional Repair of Human Donor Lungs by IL-10 Gene Therapy Science Translational Medicine, October 28, 2009; 1(4): 4ra9 - 4ra9. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Sun, R.-F. Guo, M. W. Newstead, T. J. Standiford, D. R. Macariola, and T. P. Shanley Effect of IL-10 on Neutrophil Recruitment and Survival after Pseudomonas aeruginosa Challenge Am. J. Respir. Cell Mol. Biol., July 1, 2009; 41(1): 76 - 84. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Yang, A. K. Sharma, J. Linden, I. L. Kron, and V. E. Laubach CD4+ T lymphocytes mediate acute pulmonary ischemia-reperfusion injury. J. Thorac. Cardiovasc. Surg., March 1, 2009; 137(3): 695 - 702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Yang, A. K. Sharma, M. Marshall, I. L. Kron, and V. E. Laubach NADPH Oxidase in Bone Marrow-Derived Cells Mediates Pulmonary Ischemia-Reperfusion Injury Am. J. Respir. Cell Mol. Biol., March 1, 2009; 40(3): 375 - 381. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Xu, F. Xu, and E. Barrett Metalloelastase in lungs and alveolar macrophages is modulated by extracellular substance P in mice Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L162 - L170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Elizur, T. L. Adair-Kirk, D. G. Kelley, G. L. Griffin, D. E. deMello, and R. M. Senior Tumor Necrosis Factor-{alpha} from Macrophages Enhances LPS-Induced Clara Cell Expression of Keratinocyte-Derived Chemokine Am. J. Respir. Cell Mol. Biol., January 1, 2008; 38(1): 8 - 15. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
