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Apolipoprotein C-II and lipoprotein lipase show a temporal and geographic correlation with surfactant lipid synthesis in preparation for birth.

Côté M, Provost PR, Gérard-Hudon MC, Tremblay Y - BMC Dev. Biol. (2010)

Bottom Line: The major sites of apoC-II and LPL gene expression changed over time and were found mainly in the distal epithelium at the end of gestation but not after birth.Accumulation of apoC-II in secretory granule-like structures was not systematically observed, but was found in the distal epithelium only at the end of gestation and soon after birth, mainly in epithelia with no or small lumina.We propose a model where apoC-II is retained in secretory granules in distal epithelial cells until the lumina reaches a minimum size, and is then secreted when the rate of surfactant production becomes optimal.

View Article: PubMed Central - HTML - PubMed

Affiliation: Reproduction, Perinatal and Child Health Axis, Rm T-1-49, CHUQ Research Center, Centre de Recherche en Biologie de Reproduction, Laval University, Québec City, Québec, Canada.

ABSTRACT

Background: Fatty acids are precursors in the synthesis of surfactant phospholipids. Recently, we showed expression of apolipoprotein C-II (apoC-II), the essential cofactor of lipoprotein lipase (LPL), in the fetal mouse lung and found the protein on the day of the surge of surfactant synthesis (gestation day 17.5) in secretory granule-like structures in the distal epithelium. In the present study, we will answer the following questions: Does apoC-II protein localization change according to the stage of lung development, thus according to the need in surfactant? Are LPL molecules translocated to the luminal surface of capillaries? Do the sites of apoC-II and LPL gene expression change according to the stage of lung development and to protein localization?

Results: The present study investigated whether the sites of apoC-II and LPL mRNA and protein accumulation are regulated in the mouse lung between gestation day 15 and postnatal day 10. The major sites of apoC-II and LPL gene expression changed over time and were found mainly in the distal epithelium at the end of gestation but not after birth. Accumulation of apoC-II in secretory granule-like structures was not systematically observed, but was found in the distal epithelium only at the end of gestation and soon after birth, mainly in epithelia with no or small lumina. A noticeable increase in surfactant lipid content was measured before the end of gestation day 18, which correlates temporally with the presence of apoC-II in secretory granules in distal epithelium with no or small lumina but not with large lumina. LPL was detected in capillaries at all the developmental times studied.

Conclusions: This study demonstrates that apoC-II and LPL mRNAs correlate temporally and geographically with surfactant lipid synthesis in preparation for birth and suggests that fatty acid recruitment from the circulation by apoC-II-activated LPL is regionally modulated by apoC-II secretion. We propose a model where apoC-II is retained in secretory granules in distal epithelial cells until the lumina reaches a minimum size, and is then secreted when the rate of surfactant production becomes optimal.

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Distribution of PECAM-1 and α-sma proteins in the mouse fetal lung. Mouse tissue sections isolated on GD 17.5 were subjected to immunohistochemistry using anti-PECAM-1 (A, B) or anti-α-sma (C, D) as primary antibodies. Capillaries are PECAM-1-positive. Specific staining is clearly different between the two antibodies and only the staining pattern obtained with the anti-PECAM-1 corresponds to positive signals obtained with the anti-LPL antibody in Figure 2. Scale bars, 80 μm (A, C), 20 μm (B) or 40 μm (D). C, capillaries.
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Figure 3: Distribution of PECAM-1 and α-sma proteins in the mouse fetal lung. Mouse tissue sections isolated on GD 17.5 were subjected to immunohistochemistry using anti-PECAM-1 (A, B) or anti-α-sma (C, D) as primary antibodies. Capillaries are PECAM-1-positive. Specific staining is clearly different between the two antibodies and only the staining pattern obtained with the anti-PECAM-1 corresponds to positive signals obtained with the anti-LPL antibody in Figure 2. Scale bars, 80 μm (A, C), 20 μm (B) or 40 μm (D). C, capillaries.

Mentions: In order to confirm that the LPL-positive signal corresponds to capillaries and not to α-smooth muscle actin (α-sma)-positive structures, an anti-platelet endothelial cell adhesion molecule-1 (PECAM-1) antibody was used on GD 17.5-lung tissue sections to stain capillaries. Results show that staining of capillary network (Figure 3A-B) is very similar to the positive signals identified as capillary-like structures using an anti-LPL antibody. In contrast, the use of an anti-α-sma antibody leads to a different staining profile (Figure 3C-D).


Apolipoprotein C-II and lipoprotein lipase show a temporal and geographic correlation with surfactant lipid synthesis in preparation for birth.

Côté M, Provost PR, Gérard-Hudon MC, Tremblay Y - BMC Dev. Biol. (2010)

Distribution of PECAM-1 and α-sma proteins in the mouse fetal lung. Mouse tissue sections isolated on GD 17.5 were subjected to immunohistochemistry using anti-PECAM-1 (A, B) or anti-α-sma (C, D) as primary antibodies. Capillaries are PECAM-1-positive. Specific staining is clearly different between the two antibodies and only the staining pattern obtained with the anti-PECAM-1 corresponds to positive signals obtained with the anti-LPL antibody in Figure 2. Scale bars, 80 μm (A, C), 20 μm (B) or 40 μm (D). C, capillaries.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2991289&req=5

Figure 3: Distribution of PECAM-1 and α-sma proteins in the mouse fetal lung. Mouse tissue sections isolated on GD 17.5 were subjected to immunohistochemistry using anti-PECAM-1 (A, B) or anti-α-sma (C, D) as primary antibodies. Capillaries are PECAM-1-positive. Specific staining is clearly different between the two antibodies and only the staining pattern obtained with the anti-PECAM-1 corresponds to positive signals obtained with the anti-LPL antibody in Figure 2. Scale bars, 80 μm (A, C), 20 μm (B) or 40 μm (D). C, capillaries.
Mentions: In order to confirm that the LPL-positive signal corresponds to capillaries and not to α-smooth muscle actin (α-sma)-positive structures, an anti-platelet endothelial cell adhesion molecule-1 (PECAM-1) antibody was used on GD 17.5-lung tissue sections to stain capillaries. Results show that staining of capillary network (Figure 3A-B) is very similar to the positive signals identified as capillary-like structures using an anti-LPL antibody. In contrast, the use of an anti-α-sma antibody leads to a different staining profile (Figure 3C-D).

Bottom Line: The major sites of apoC-II and LPL gene expression changed over time and were found mainly in the distal epithelium at the end of gestation but not after birth.Accumulation of apoC-II in secretory granule-like structures was not systematically observed, but was found in the distal epithelium only at the end of gestation and soon after birth, mainly in epithelia with no or small lumina.We propose a model where apoC-II is retained in secretory granules in distal epithelial cells until the lumina reaches a minimum size, and is then secreted when the rate of surfactant production becomes optimal.

View Article: PubMed Central - HTML - PubMed

Affiliation: Reproduction, Perinatal and Child Health Axis, Rm T-1-49, CHUQ Research Center, Centre de Recherche en Biologie de Reproduction, Laval University, Québec City, Québec, Canada.

ABSTRACT

Background: Fatty acids are precursors in the synthesis of surfactant phospholipids. Recently, we showed expression of apolipoprotein C-II (apoC-II), the essential cofactor of lipoprotein lipase (LPL), in the fetal mouse lung and found the protein on the day of the surge of surfactant synthesis (gestation day 17.5) in secretory granule-like structures in the distal epithelium. In the present study, we will answer the following questions: Does apoC-II protein localization change according to the stage of lung development, thus according to the need in surfactant? Are LPL molecules translocated to the luminal surface of capillaries? Do the sites of apoC-II and LPL gene expression change according to the stage of lung development and to protein localization?

Results: The present study investigated whether the sites of apoC-II and LPL mRNA and protein accumulation are regulated in the mouse lung between gestation day 15 and postnatal day 10. The major sites of apoC-II and LPL gene expression changed over time and were found mainly in the distal epithelium at the end of gestation but not after birth. Accumulation of apoC-II in secretory granule-like structures was not systematically observed, but was found in the distal epithelium only at the end of gestation and soon after birth, mainly in epithelia with no or small lumina. A noticeable increase in surfactant lipid content was measured before the end of gestation day 18, which correlates temporally with the presence of apoC-II in secretory granules in distal epithelium with no or small lumina but not with large lumina. LPL was detected in capillaries at all the developmental times studied.

Conclusions: This study demonstrates that apoC-II and LPL mRNAs correlate temporally and geographically with surfactant lipid synthesis in preparation for birth and suggests that fatty acid recruitment from the circulation by apoC-II-activated LPL is regionally modulated by apoC-II secretion. We propose a model where apoC-II is retained in secretory granules in distal epithelial cells until the lumina reaches a minimum size, and is then secreted when the rate of surfactant production becomes optimal.

Show MeSH
Related in: MedlinePlus