PMID- 17416740
OWN - NLM
STAT- MEDLINE
DCOM- 20070829
LR  - 20200930
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 293
IP  - 1
DP  - 2007 Jul
TI  - Proinflammatory response of alveolar epithelial cells is enhanced by alveolar 
      macrophage-produced TNF-alpha during pulmonary ischemia-reperfusion injury.
PG  - L105-13
AB  - 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 hypoxia-reoxygenation (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-1alpha, 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.
FAU - Sharma, Ashish K
AU  - Sharma AK
AD  - Department of Surgery, University of Virginia Health System, Charlottesville, 
      Virginia 22908, USA.
FAU - Fernandez, Lucas G
AU  - Fernandez LG
FAU - Awad, Alaa S
AU  - Awad AS
FAU - Kron, Irving L
AU  - Kron IL
FAU - Laubach, Victor E
AU  - Laubach VE
LA  - eng
GR  - R01-HL-077301/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070406
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Chemokines)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Cell Communication
MH  - Cell Hypoxia
MH  - Cells, Cultured
MH  - Chemokines/metabolism
MH  - Epithelial Cells/*pathology
MH  - *Inflammation
MH  - Macrophages, Alveolar/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pulmonary Alveoli/*pathology
MH  - Reperfusion Injury/chemically induced/*metabolism/*pathology
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 2007/04/10 09:00
MHDA- 2007/08/30 09:00
CRDT- 2007/04/10 09:00
PHST- 2007/04/10 09:00 [pubmed]
PHST- 2007/08/30 09:00 [medline]
PHST- 2007/04/10 09:00 [entrez]
AID - 00470.2006 [pii]
AID - 10.1152/ajplung.00470.2006 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2007 Jul;293(1):L105-13. doi: 
      10.1152/ajplung.00470.2006. Epub 2007 Apr 6.