2006 Fiscal Year Final Research Report Summary
RAGE : Its pahotphysiological role in the lung injury and a biomarker of acute lung injury
| Project/Area Number |
17591618
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
UCHIDA Tokujiro Tokyo Medical and Dental Univ., Assistant Professor, 医学部附属病院, 講師 (40262183)
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| Project Period (FY) |
2005 – 2006
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| Keywords | lung injury / biomarker / pulmonary edema |
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| Research Abstract |
Rationale : Receptor for advanced glycation end-products (RAGE) is one of the alveolar type I cell associated proteins in the lung.
Objectives : To test the hypothesis that RAGE is a marker of alveolar epithelial type I cell injury.
Methods : Rats were instilled intratracheally with either 10 mg/kg lipopolysaccharide (LPS) or hydrochloric acid. RAGE levels were measured in the bronchoalveolar lavage (BAL) and serum in the rats and in the pulmonary edema fluid and plasma from patients with acute lung injury (ALI) (n=22) and hydrostatic pulmonary edema (n=11).
Main Results : In the rat lung injury studies, RAGE was released into the BAL and serum as a single soluble isoform sized 〜48 kD. The elevated levels of RAGE in the BAL correlated well with the severity of experimentally induced lung injury. In the human studies, the RAGE level in the pulmonary edema fluid was significantly higher than the plasma level (p<0.0001). The median edema fluid / plasma ratio of RAGE levels was 105 (IQR;55-243). The RAGE levels in the pulmonary edema fluid from patients with ALI were higher than the levels from patients with hydrostatic pulmonary edema (p<0.05), and the plasma RAGE level in patients with ALI were significantly higher than the healthy volunteers (p<0.001) or patients with hydrostatic pulmonary edema (p<0.05).
Conclusion : RAGE is a marker of type I alveolar epithelial cell injury based on experimental studies in rats as well as in patients with acute lung injury.
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