Expression of Plasma Phospholipid Transfer Protein mRNA in Normal and Emphysematous Lungs and Regulation by Hypoxia

Abstract

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.

Interaction of phospholipid transfer protein with human tear fluid mucins

“…In plasma, PLTP transfers phospholipids, but not neutral lipids, between lipoprotein particles ( 13 ). The PLTP gene is also highly expressed in alveolar type II cells and is induced during hypoxia and in emphysema ( 14 ), indicating surface protective properties. Notably human lung tissue, where PLTP is found in an air-water environment (i.e., similar to tear fl uid), displays high PLTP expression levels compared with other tissues.…”

“…The complex, also containing trace amounts of 14 [C]DPPC, was incubated together with purifi ed PLTP and PLTP distribution was investigated using size exclusion chromatography (SEC). Approximately 80% of the radioactive label was recovered from the BSM-PC complex after cholate dialysis.…”

“…In brief, 1.27 mg of egg yolk phosphatidylcholine [EggPC, Sigma, 100 mg/ml stock in chloroform methanol, 9:1 (v/v)] and approximately 750 cpm of 14 [C]DPPC in toluene (Amersham CFA, UK) per nmol of phospholipids were added to a glass vial. The organic solvent was evaporated under nitrogen at room temperature, 1 ml of BSM or OVM (1 mg/ml in PBS) was added, and the mixture was carefully vortexed.…”

Effect of Qingyitang on activity of intracellular Ca2+-Mg2+-ATPase in rats with acute pancreatitis

“…Intracellular calcium overload further facilitated the release of pro-inflammatory mediators, which would cause strong contraction and thrombosis of microcirculation. Thus energy metabolism in tissues was disordered and ATP production was reduced [12][13][14][15][16] . In addition, large quantities of free radicals produced during acute pancreatitis would cause phospholipids re-distribution in cell membrane.…”

Dry Eye Symptoms Are Increased in Mice Deficient in Phospholipid Transfer Protein (PLTP)

“…19 The human lung tissue, where PLTP is found at an air-water environment (ie, similar to the tear fluid), displays high levels of PLTP compared with other tissues. PLTP is highly expressed in alveolar type II cells, and, notably, is induced during hypoxia and in emphysema, 20 suggesting novel surface protective properties of this molecule. Recently, we elucidated the mechanism of PLTP-facilitated phospholipid transfer 21 and very recently showed that PLTP interacts with human tear fluid mucins.…”