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Published ahead of print on July 28, 2004, doi:10.1164/rccm.200307-908OC

Am. J. Respir. Crit. Care Med., Volume 170, Number 11, December 2004, 1158-1163

A more recent version of this article appeared on December 1, 2004
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Submitted on July 10, 2003
Accepted on July 27, 2004

Cells Derived from the Circulation Contribute to the Repair of Lung Injury

Shinji Abe1, Craig Boyer2, Xiangde Liu1, Fu Qiang Wen1, Tetsu Kobayashi1, Qiuhong Fang1, Xingqi Wang1, Mitsuyoshi Hashimoto1, J. Graham Sharp2, and Stephen I Rennard1*

1 Department of Internal Medicine, Pulmonary and Critical Care Medicine Section, University of Nebraska Medical Center, Omaha, NE, USA, 2 Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA

* To whom correspondence should be addressed. E-mail: srennard{at}unmc.edu.

Bone marrow (stem/progenitor) cells have been shown to 'differentiate' into cells in multiple tissues, including lung. A low number of hematopoietic stem/progenitor cells also circulates in peripheral blood. The physiological roles of these cells are still uncertain. This study was designed to test, using parabiotic mice that were joined surgically, if stem/progenitor cells in blood contributed to the regeneration of lung following injury. Parabiotic mice were generated surgically by joining green fluorescent protein transgenic mice and wild-type littermates. These mice developed a common circulation (~50% green cells in blood) by 2 weeks after surgery. The wild-type mouse was either uninjured, lethally irradiated, received intra-tracheal elastase or the combination of radiation with intra-tracheal elastase injection. Radiation or the combination of radiation with elastase significantly increased the proportion of bright green cells in the lungs of the wild-type mice. Morphologically, interstitial monocytes/macrophages, subepithelial fibroblast-like interstitial cells and additionally type I alveolar epithelial cells immunostained for green fluorescent protein in wild-type mice. About 5-20% of lung fibroblasts primary cultured from injured wild-type mice were green fluorescent protein expressing cells, indicating their blood derivation. This study demonstrates that stem/progenitor cells in blood contribute to the repair of lung injury in irradiated mice.
Key words: stem/progenitor cell in blood, parabiosis, lung repair




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