Abstract |
A critical step in the pathogenesis of acute lung injury (ALI) is excessive recruitment of polymorphonuclear neutrophils (PMNs) into the lungs, causing significant collateral tissue damage. Defining the molecular and cellular steps that control neutrophil infiltration and activation during ALI is therefore of important therapeutic relevance. Based on previous findings implicating the transcription factor Tbet in mucosal Th1-inflammation, we hypothesized a detrimental role for Tbet during ALI. In line with our hypothesis, initial studies of endotoxin-induced lung injury revealed a marked protection of Tbet-/- mice, including attenuated neutrophilia compared to WT counterparts. Surprisingly, subsequent studies identified natural killer (NK) cells as the major source of pulmonary Tbet during ALI. In addition, a chemokine screen suggested that mature Tbet+ NK-cells are critical for the production of pulmonary CXCL1 and -2, thereby contributing to pulmonary PMN recruitment. Indeed, both NK-cell Ab depletion and adoptive transfer studies provide evidence for NK cells in the orchestration of neutrophil recruitment during endotoxin-induced ALI. Taken together, these findings identify a novel role for Tbet+ NK-cells in initiating the early events of noninfectious pulmonary inflammation.
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Authors | Sandra Hoegl, Heidi Ehrentraut, Kelley S Brodsky, Francisco Victorino, Lucy Golden-Mason, Holger K Eltzschig, Eóin N McNamee |
Journal | Journal of leukocyte biology
(J Leukoc Biol)
Vol. 101
Issue 2
Pg. 471-480
(02 2017)
ISSN: 1938-3673 [Electronic] United States |
PMID | 27601626
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
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Copyright | © Society for Leukocyte Biology. |
Chemical References |
- Antibodies
- Cytokines
- Inflammation Mediators
- Lipopolysaccharides
- Receptors, Interleukin-8B
- T-Box Domain Proteins
- T-box transcription factor TBX21
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Topics |
- Acute Lung Injury
(complications, immunology, pathology)
- Adoptive Transfer
- Animals
- Antibodies
(metabolism)
- Cytokines
(metabolism)
- Inflammation Mediators
(metabolism)
- Killer Cells, Natural
(immunology)
- Lipopolysaccharides
- Mice, Inbred C57BL
- Neutrophil Infiltration
(immunology)
- Pneumonia
(complications, immunology, pathology)
- Receptors, Interleukin-8B
(metabolism)
- T-Box Domain Proteins
(metabolism)
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