期刊
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
卷 293, 期 1, 页码 L105-L113出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00470.2006
关键词
cytokines; chemokines
资金
- NHLBI NIH HHS [R01-HL-077301] Funding Source: Medline
Pulmonary ischemia-reperfusion ( IR) injury entails acute activation of alveolar macrophages followed by neutrophil sequestration. Although proinflammatory cytokines and chemokines such as TNF-alpha and monocyte chemoattractant protein-1 ( 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-alpha further induces alveolar epithelial cells to produce key chemokines that could then contribute to subsequent lung injury through the recruitment of neutrophils. Cultured RAW264.7 macrophages and MLE-12 alveolar epithelial cells were subjected to acute hypoxiareoxygenation ( H/R) as an in vitro model of pulmonary IR. H/R (3 h/1 h) significantly induced KC, MCP- 1, macrophage inflammatory protein-2 ( MIP-2), RANTES, and IL-6 ( but not TNF-alpha) by MLE-12 cells, whereas H/R induced TNF-alpha, MCP-1, RANTES, MIP-1 alpha, 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 coculture methods, the specific production of TNF-alpha by H/R-exposed RAW264.7 cells significantly induced proinflammatory cytokine/ chemokine expression ( KC, MCP- 1, MIP- 2, RANTES, and IL- 6) by MLE- 12 cells. Collectively, these results demonstrate that alveolar type II cells, in conjunction with alveolar macrophage- produced TNF-alpha, 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.
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