J. Lipid Res.
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A more recent version of this article appeared on December 1, 2004

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J. Lipid Res., doi:10.1194/jlr.M400302-JLR200
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Submitted on August 9, 2004
Revised on September 16, 2004
Accepted on September 17, 2004

Serum cholestenoic acid as a potential marker of pulmonary cholesterol homeostasis: Elevated levels in patients with pulmonary alveolar proteinosis

Steve Meaney, Tracey L. Bonfield, Magnus Hansson, Amir Babiker, Mani S. Kavuru, and Mary Jane Thomassen

Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital - Huddinge, Stockholm 14186

Corresponding Author: steve.meaney{at}labmed.ki.se

Conversion of cholesterol into the more polar metabolites 27-hydroxycholesterol and cholestenoic acid by the cytochrome P450 sterol 27-hydroxylase is a cholesterol removal mechanism employed by almost all cells. Most of the cholestenoic acid present in the circulation originates from the lung, and it has been suggested that sterol 27-hydroxylase is of particular importance for cholesterol homeostasis in this organ. As an example of pulmonary cholesterol accumulation a known disorder of surfactant homeostasis, Pulmonary Alveolar Proteinosis (PAP), was studied. Analysis of broncheoalveolar lavage fluid from PAP patients revealed a significant accumulation of the cholesterol metabolites cholestenoic acid and 27-hydroxycholesterol. This pattern was recapitulated in serum, with a significant increase in the levels of both cholestenoic acid (p = 0.003) and 27-hydroxycholesterol (p=0.017) in the PAP patients compared to the healthy controls. Analysis of PAP alveolar macrophages did not reveal a significant change in mRNA expression levels of either sterol 27-hydroxylase or the cholesterol esterifying enzyme acyl-CoA:cholesterol acyltransferase-1. These results are consistent with the contention that substrate availability, rather than enzyme expression is the key factor in regulating the production of cholestenoic acid by the lung, and that serum cholestenoic acid may be a marker of pulmonary cholesterol homeostasis.


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