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J Biol Chem, Vol. 273, Issue 25, 15714-15718, June 19, 1998
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From the The lung is the major site expressing plasma
phospholipid transfer protein (PLTP) mRNA in humans and mice,
suggesting that this protein might have an important role in
maintaining normal function of this organ. In the lung of human
collagenase transgenic mice, an emphysematous animal model, PLTP
mRNA was 3-fold higher than in control mice. However, the mRNA
in other tissues was not changed. To further assess the expression and
function of PLTP, we measured PLTP mRNA level in lung tissue of two
emphysematous patients and found that the mRNA was 4-fold higher
than in control subjects. In situ hybridization on mouse
lung suggested positive staining in alveolar type II epithelial cells.
In addition, immortalized rat alveolar pre-type II epithelial cells and
freshly isolated mature rat alveolar type II epithelial cells both
highly expressed PLTP mRNA, and the former cells actively secreted
PLTP activity into the medium. To examine the possible mechanisms
leading to high levels of PLTP expression in vivo, we
exposed the pre-type II cells to hypoxia and demonstrated induction of
PLTP mRNA and a coordinate increase in secreted PLTP activity.
Thus, the PLTP gene is highly expressed in alveolar type II epithelial
cells and is induced during hypoxia and in emphysema. These
observations suggest that a hypoxic stimulus occurring in emphysema may
be a novel mechanism that contributes to enhanced expression of
PLTP.
Division of Molecular Medicine, Department
of Medicine, Columbia University, New York 10032 and the
¶ Department of Internal Medicine and Department of Veterans
Affairs Medical Center, The University of Iowa College of Medicine,
Iowa City, Iowa 52242
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