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Whole‐body hypoxic preconditioning reduces hypoxia‐induced lung injury through preferential protection of alveolar type I cells
Author(s) -
Zhang Shelley X.L.,
Miller James J.,
Zhao Wei,
Guo Shang Z.,
Gozal David,
Wang Yang
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a404-b
Subject(s) - lactate dehydrogenase , hypoxia (environmental) , lung , von willebrand factor , chemistry , pulmonary edema , creatine kinase , andrology , medicine , endocrinology , biochemistry , oxygen , enzyme , organic chemistry , platelet
Whole‐body hypoxic preconditioning (WHPC) prolongs survival of mice exposed to hypoxia by attenuating the development of pulmonary edema and thus preserving gas exchange. However, the cellular mechanism(s) of this protection remain unclear. The objective of this study was to identify the cellular target(s) of WHPC in the lung. Conscious mice were exposed to hypoxia (7% O2) for 6 h with or without pretreatment by WHPC. We found that hypoxia caused severe lung injury as evidenced by increases in lavage lactate dehydrogenase (LDH, 179.3+/−39.2 vs. controls at 64.9+/−6.7 U/L, n=8, p<0.01) and creatine kinase activities (CK, 392.9+/−100.5 vs. controls at 73.0+/−9.3 U/L, n=8, p<0.01). Pretreatment by WHPC minimized the release of these general cytotoxicity markers in the lavage (LDH 68.9+/−7.1 U/L; CK 120.6+/−35.3 U/L; n=8, p<0.05 vs. hypoxia alone for both). WHPC also reduced the release of these markers to the circulation, but to a lesser degree. We further analyzed type‐I cell‐specific (caveolin 1 and 3) and type‐II cell‐specific markers (surfactant‐associated proteins A and B) in the lavage and an endothelium‐specific marker (von Willebrand Factor Antigen) in blood samples from the right and left ventricles. We found that WHPC substantially reduced the release of type‐I cell‐specific markers, moderately reduced the lung release of the endothelial marker, but had little effect on type‐II cell‐specific markers. Additional analyses using cytology and light and electron microscopy revealed similar findings. We conclude that WHPC preferentially increases the resistance of type‐I cells to hypoxia, and, thereby reduces hypoxic lung injury. Supported by NIH (RO1HL074369).