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Lamonica, Giulia (2013) Stable isotope tracers to estimate lung surfactant metabolism in vivo. [Tesi di dottorato]

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Abstract (inglese)

Aim of this thesis was to apply the stable isotopes technique to study pulmonary surfactant kinetics.
Lung surfactant is essential to live, because it prevents the alveoli to collapse during normal breathing. Lung surfactant is composed of lipids and specific proteins, and nowadays it is well known that alterations on the composition and amount of surfactant are involved in acute and chronic lung diseases.
This work presents two studies about lung surfactant kinetics.
The first one is about the synthesis of disaturated phosphatidylcholine, the main lipid in the pulmonary surfactant system, in a murine model of unilateral acid injury.
The second one explains an optimized procedure to evaluate surfactant protein B synthesis and a novel method to study surfactant protein C synthesis in both infants and adults, each with stable isotopes technique

Abstract (italiano)

Obiettivo di questa tesi è stato quello di applicare l’uso degli isotopi stabili come traccianti metabolici allo studio del metabolismo del surfattante polmonare.
Il surfattante polmonare è una sostanza fondamentale per vivere in quanto impedisce agli alveoli di collassare durante l’atto respiratorio. Il surfattante polmonare è composto da lipidi e proteine specifiche, ed è ormai noto che alterazioni nella composizione e nella quantità del surfattante polmonare sono presenti nella malattia respiratoria acuta e cronica.
In questo lavoro vengono presentati due studi sulla cinetica del surfattante polmonare: il primo riguarda la sintesi del lipide maggiormente presente nel surfattante, ovvero la fosfatidilcolina disatura, in una condizione di danno unilaterale da acido in un modello murino.
Il secondo studio riguarda un metodo ottimizzato per misurare la sintesi della proteina B del surfattante e un nuovo metodo per valutare, sempre con l’utilizzo degli isotopi stabili, la sintesi della proteina C del surfattante in bambini e adulti

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Tipo di EPrint:Tesi di dottorato
Relatore:Cogo, Paola
Dottorato (corsi e scuole):Ciclo 25 > Scuole 25 > MEDICINA DELLO SVILUPPO E SCIENZE DELLA PROGRAMMAZIONE > EMATOONCOLOGIA, IMMUNOLOGIA E GENETICA
Data di deposito della tesi:27 Gennaio 2013
Anno di Pubblicazione:27 Gennaio 2013
Parole chiave (italiano / inglese):lung mass spectrometry, surfactant, aspiration, pneumonia, stable isotopes, polmoni, surfattante, polmonite, aspirazione, isotopi stabili, spettrometria di massa
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/38 Pediatria generale e specialistica
Struttura di riferimento:Dipartimenti > Dipartimento di Salute della Donna e del Bambino
Codice ID:5549
Depositato il:16 Ott 2013 10:02
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Bibliografia

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CHAPTER 1 Cerca con Google

1. Berthiaume Y, Voisin G, Dagenais A. The alveolar type I cells: the new knight of the alveolus? J Physiol 2006: 572(Pt 3): 609-610. Cerca con Google

2. Casals C, Canadas O. Role of lipid ordered/disordered phase coexistence in pulmonary surfactant function. Biochim Biophys Acta 2012: 1818(11): 2550-2562. Cerca con Google

3. Griese M. Pulmonary surfactant in health and human lung diseases: state of the art. Eur Respir J 1999: 13(6): 1455-1476. Cerca con Google

4. Enhorning G. Surfactant in airway disease. Chest 2008: 133(4): 975-980. Cerca con Google

5. Haagsman HP, van Golde LM. Synthesis and assembly of lung surfactant. Annu Rev Physiol 1991: 53: 441-464. Cerca con Google

6. Batenburg JJ. Surfactant phospholipids: synthesis and storage. Am J Physiol 1992: 262(4 Pt 1): L367-385. Cerca con Google

7. Ridsdale R, Na CL, Xu Y, Greis KD, Weaver T. Comparative proteomic analysis of lung lamellar bodies and lysosome-related organelles. PLoS One 2011: 6(1): e16482. Cerca con Google

8. Hook GE. Alveolar proteinosis and phospholipidoses of the lungs. Toxicol Pathol 1991: 19(4 Pt 1): 482-513. Cerca con Google

9. Sullivan LC, Orgeig S, Daniels CB. Control of the development of the pulmonary surfactant system in the saltwater crocodile, Crocodylus porosus. Am J Physiol Regul Integr Comp Physiol 2002: 283(5): R1164-1176. Cerca con Google

10. Holm BA, Wang Z, Egan EA, Notter RH. Content of dipalmitoyl phosphatidylcholine in lung surfactant: ramifications for surface activity. Pediatr Res 1996: 39(5): 805-811. Cerca con Google

11. Hallman M, Enhorning G, Possmayer F. Composition and surface activity of normal and phosphatidylglycerol-deficient lung surfactant. Pediatr Res 1985: 19(3): 286-292. Cerca con Google

12. Numata M, Chu HW, Dakhama A, Voelker DR. Pulmonary surfactant phosphatidylglycerol inhibits respiratory syncytial virus-induced inflammation and infection. Proc Natl Acad Sci U S A 2010: 107(1): 320-325. Cerca con Google

13. Agassandian M, Mallampalli RK. Surfactant phospholipid metabolism. Biochim Biophys Acta 2012. Cerca con Google

14. Lu Z, Gu Y, Rooney SA. Transcriptional regulation of the lung fatty acid synthase gene by glucocorticoid, thyroid hormone and transforming growth factor-beta 1. Biochim Biophys Acta 2001: 1532(3): 213-222. Cerca con Google

15. Rooney SA. Regulation of surfactant secretion. Comp Biochem Physiol A Mol Integr Physiol 2001: 129(1): 233-243. Cerca con Google

16. Xu X, McCormick-Shannon K, Voelker DR, Mason RJ. KGF increases SP-A and SP-D mRNA levels and secretion in cultured rat alveolar type II cells. Am J Respir Cell Mol Biol 1998: 18(2): 168-178. Cerca con Google

17. Crouch E, Persson A, Chang D, Parghi D. Surfactant protein D. Increased accumulation in silica-induced pulmonary lipoproteinosis. Am J Pathol 1991: 139(4): 765-776. Cerca con Google

18. Voorhout WF, Veenendaal T, Kuroki Y, Ogasawara Y, van Golde LM, Geuze HJ. Immunocytochemical localization of surfactant protein D (SP-D) in type II cells, Clara cells, and alveolar macrophages of rat lung. J Histochem Cytochem 1992: 40(10): 1589-1597. Cerca con Google

19. Gobran LI, Rooney SA. Adenylate cyclase-coupled ATP receptor and surfactant secretion in type II pneumocytes from newborn rats. Am J Physiol 1997: 272(2 Pt 1): L187-196. Cerca con Google

20. Mason RJ, Voelker DR. Regulatory mechanisms of surfactant secretion. Biochim Biophys Acta 1998: 1408(2-3): 226-240. Cerca con Google

21. Zimmermann LJ, Janssen DJ, Tibboel D, Hamvas A, Carnielli VP. Surfactant metabolism in the neonate. Biol Neonate 2005: 87(4): 296-307. Cerca con Google

22. Schmitz G, Muller G. Structure and function of lamellar bodies, lipid-protein complexes involved in storage and secretion of cellular lipids. J Lipid Res 1991: 32(10): 1539-1570. Cerca con Google

23. Bohlin K, Merchak A, Spence K, Patterson BW, Hamvas A. Endogenous surfactant metabolism in newborn infants with and without respiratory failure. Pediatr Res 2003: 54(2): 185-191. Cerca con Google

24. Hall SB, Lu RZ, Venkitaraman AR, Hyde RW, Notter RH. Inhibition of pulmonary surfactant by oleic acid: mechanisms and characteristics. J Appl Physiol 1992: 72(5): 1708-1716. Cerca con Google

25. Schmidt R, Meier U, Yabut-Perez M, Walmrath D, Grimminger F, Seeger W, Gunther A. Alteration of fatty acid profiles in different pulmonary surfactant phospholipids in acute respiratory distress syndrome and severe pneumonia. Am J Respir Crit Care Med 2001: 163(1): 95-100. Cerca con Google

26. Jobe AH. Mechanisms to explain surfactant responses. Biol Neonate 2006: 89(4): 298-302. Cerca con Google

27. Bae CW, Takahashi A, Chida S, Sasaki M. Morphology and function of pulmonary surfactant inhibited by meconium. Pediatr Res 1998: 44(2): 187-191. Cerca con Google

28. Cayabyab RG, Kwong K, Jones C, Minoo P, Durand M. Lung inflammation and pulmonary function in infants with meconium aspiration syndrome. Pediatr Pulmonol 2007: 42(10): 898-905. Cerca con Google

CHAPTER 2 Cerca con Google

1. Berthiaume Y, Voisin G, Dagenais A. The alveolar type I cells: the new knight of the alveolus? J Physiol 2006: 572(Pt 3): 609-610. Cerca con Google

2. Casals C, Canadas O. Role of lipid ordered/disordered phase coexistence in pulmonary surfactant function. Biochim Biophys Acta 2012: 1818(11): 2550-2562. Cerca con Google

3. Griese M. Pulmonary surfactant in health and human lung diseases: state of the art. Eur Respir J 1999: 13(6): 1455-1476. Cerca con Google

4. Enhorning G. Surfactant in airway disease. Chest 2008: 133(4): 975-980. Cerca con Google

5. Haagsman HP, van Golde LM. Synthesis and assembly of lung surfactant. Annu Rev Physiol 1991: 53: 441-464. Cerca con Google

6. Batenburg JJ. Surfactant phospholipids: synthesis and storage. Am J Physiol 1992: 262(4 Pt 1): L367-385. Cerca con Google

7. Ridsdale R, Na CL, Xu Y, Greis KD, Weaver T. Comparative proteomic analysis of lung lamellar bodies and lysosome-related organelles. PLoS One 2011: 6(1): e16482. Cerca con Google

8. Hook GE. Alveolar proteinosis and phospholipidoses of the lungs. Toxicol Pathol 1991: 19(4 Pt 1): 482-513. Cerca con Google

9. Sullivan LC, Orgeig S, Daniels CB. Control of the development of the pulmonary surfactant system in the saltwater crocodile, Crocodylus porosus. Am J Physiol Regul Integr Comp Physiol 2002: 283(5): R1164-1176. Cerca con Google

10. Holm BA, Wang Z, Egan EA, Notter RH. Content of dipalmitoyl phosphatidylcholine in lung surfactant: ramifications for surface activity. Pediatr Res 1996: 39(5): 805-811. Cerca con Google

11. Hallman M, Enhorning G, Possmayer F. Composition and surface activity of normal and phosphatidylglycerol-deficient lung surfactant. Pediatr Res 1985: 19(3): 286-292. Cerca con Google

12. Numata M, Chu HW, Dakhama A, Voelker DR. Pulmonary surfactant phosphatidylglycerol inhibits respiratory syncytial virus-induced inflammation and infection. Proc Natl Acad Sci U S A 2010: 107(1): 320-325. Cerca con Google

13. Agassandian M, Mallampalli RK. Surfactant phospholipid metabolism. Biochim Biophys Acta 2012. Cerca con Google

14. Lu Z, Gu Y, Rooney SA. Transcriptional regulation of the lung fatty acid synthase gene by glucocorticoid, thyroid hormone and transforming growth factor-beta 1. Biochim Biophys Acta 2001: 1532(3): 213-222. Cerca con Google

15. Rooney SA. Regulation of surfactant secretion. Comp Biochem Physiol A Mol Integr Physiol 2001: 129(1): 233-243. Cerca con Google

16. Xu X, McCormick-Shannon K, Voelker DR, Mason RJ. KGF increases SP-A and SP-D mRNA levels and secretion in cultured rat alveolar type II cells. Am J Respir Cell Mol Biol 1998: 18(2): 168-178. Cerca con Google

17. Crouch E, Persson A, Chang D, Parghi D. Surfactant protein D. Increased accumulation in silica-induced pulmonary lipoproteinosis. Am J Pathol 1991: 139(4): 765-776. Cerca con Google

18. Voorhout WF, Veenendaal T, Kuroki Y, Ogasawara Y, van Golde LM, Geuze HJ. Immunocytochemical localization of surfactant protein D (SP-D) in type II cells, Clara cells, and alveolar macrophages of rat lung. J Histochem Cytochem 1992: 40(10): 1589-1597. Cerca con Google

19. Gobran LI, Rooney SA. Adenylate cyclase-coupled ATP receptor and surfactant secretion in type II pneumocytes from newborn rats. Am J Physiol 1997: 272(2 Pt 1): L187-196. Cerca con Google

20. Mason RJ, Voelker DR. Regulatory mechanisms of surfactant secretion. Biochim Biophys Acta 1998: 1408(2-3): 226-240. Cerca con Google

21. Zimmermann LJ, Janssen DJ, Tibboel D, Hamvas A, Carnielli VP. Surfactant metabolism in the neonate. Biol Neonate 2005: 87(4): 296-307. Cerca con Google

22. Schmitz G, Muller G. Structure and function of lamellar bodies, lipid-protein complexes involved in storage and secretion of cellular lipids. J Lipid Res 1991: 32(10): 1539-1570. Cerca con Google

23. Bohlin K, Merchak A, Spence K, Patterson BW, Hamvas A. Endogenous surfactant metabolism in newborn infants with and without respiratory failure. Pediatr Res 2003: 54(2): 185-191. Cerca con Google

24. Hall SB, Lu RZ, Venkitaraman AR, Hyde RW, Notter RH. Inhibition of pulmonary surfactant by oleic acid: mechanisms and characteristics. J Appl Physiol 1992: 72(5): 1708-1716. Cerca con Google

25. Schmidt R, Meier U, Yabut-Perez M, Walmrath D, Grimminger F, Seeger W, Gunther A. Alteration of fatty acid profiles in different pulmonary surfactant phospholipids in acute respiratory distress syndrome and severe pneumonia. Am J Respir Crit Care Med 2001: 163(1): 95-100. Cerca con Google

26. Jobe AH. Mechanisms to explain surfactant responses. Biol Neonate 2006: 89(4): 298-302. Cerca con Google

27. Bae CW, Takahashi A, Chida S, Sasaki M. Morphology and function of pulmonary surfactant inhibited by meconium. Pediatr Res 1998: 44(2): 187-191. Cerca con Google

28. Cayabyab RG, Kwong K, Jones C, Minoo P, Durand M. Lung inflammation and pulmonary function in infants with meconium aspiration syndrome. Pediatr Pulmonol 2007: 42(10): 898-905. Cerca con Google

CHAPTER 3 Cerca con Google

1. Berthiaume Y, Voisin G, Dagenais A. The alveolar type I cells: the new knight of the alveolus? J Physiol 2006: 572(Pt 3): 609-610. Cerca con Google

2. Casals C, Canadas O. Role of lipid ordered/disordered phase coexistence in pulmonary surfactant function. Biochim Biophys Acta 2012: 1818(11): 2550-2562. Cerca con Google

3. Griese M. Pulmonary surfactant in health and human lung diseases: state of the art. Eur Respir J 1999: 13(6): 1455-1476. Cerca con Google

4. Enhorning G. Surfactant in airway disease. Chest 2008: 133(4): 975-980. Cerca con Google

5. Haagsman HP, van Golde LM. Synthesis and assembly of lung surfactant. Annu Rev Physiol 1991: 53: 441-464. Cerca con Google

6. Batenburg JJ. Surfactant phospholipids: synthesis and storage. Am J Physiol 1992: 262(4 Pt 1): L367-385. Cerca con Google

7. Ridsdale R, Na CL, Xu Y, Greis KD, Weaver T. Comparative proteomic analysis of lung lamellar bodies and lysosome-related organelles. PLoS One 2011: 6(1): e16482. Cerca con Google

8. Hook GE. Alveolar proteinosis and phospholipidoses of the lungs. Toxicol Pathol 1991: 19(4 Pt 1): 482-513. Cerca con Google

9. Sullivan LC, Orgeig S, Daniels CB. Control of the development of the pulmonary surfactant system in the saltwater crocodile, Crocodylus porosus. Am J Physiol Regul Integr Comp Physiol 2002: 283(5): R1164-1176. Cerca con Google

10. Holm BA, Wang Z, Egan EA, Notter RH. Content of dipalmitoyl phosphatidylcholine in lung surfactant: ramifications for surface activity. Pediatr Res 1996: 39(5): 805-811. Cerca con Google

11. Hallman M, Enhorning G, Possmayer F. Composition and surface activity of normal and phosphatidylglycerol-deficient lung surfactant. Pediatr Res 1985: 19(3): 286-292. Cerca con Google

12. Numata M, Chu HW, Dakhama A, Voelker DR. Pulmonary surfactant phosphatidylglycerol inhibits respiratory syncytial virus-induced inflammation and infection. Proc Natl Acad Sci U S A 2010: 107(1): 320-325. Cerca con Google

13. Agassandian M, Mallampalli RK. Surfactant phospholipid metabolism. Biochim Biophys Acta 2012. Cerca con Google

14. Lu Z, Gu Y, Rooney SA. Transcriptional regulation of the lung fatty acid synthase gene by glucocorticoid, thyroid hormone and transforming growth factor-beta 1. Biochim Biophys Acta 2001: 1532(3): 213-222. Cerca con Google

15. Rooney SA. Regulation of surfactant secretion. Comp Biochem Physiol A Mol Integr Physiol 2001: 129(1): 233-243. Cerca con Google

16. Xu X, McCormick-Shannon K, Voelker DR, Mason RJ. KGF increases SP-A and SP-D mRNA levels and secretion in cultured rat alveolar type II cells. Am J Respir Cell Mol Biol 1998: 18(2): 168-178. Cerca con Google

17. Crouch E, Persson A, Chang D, Parghi D. Surfactant protein D. Increased accumulation in silica-induced pulmonary lipoproteinosis. Am J Pathol 1991: 139(4): 765-776. Cerca con Google

18. Voorhout WF, Veenendaal T, Kuroki Y, Ogasawara Y, van Golde LM, Geuze HJ. Immunocytochemical localization of surfactant protein D (SP-D) in type II cells, Clara cells, and alveolar macrophages of rat lung. J Histochem Cytochem 1992: 40(10): 1589-1597. Cerca con Google

19. Gobran LI, Rooney SA. Adenylate cyclase-coupled ATP receptor and surfactant secretion in type II pneumocytes from newborn rats. Am J Physiol 1997: 272(2 Pt 1): L187-196. Cerca con Google

20. Mason RJ, Voelker DR. Regulatory mechanisms of surfactant secretion. Biochim Biophys Acta 1998: 1408(2-3): 226-240. Cerca con Google

21. Zimmermann LJ, Janssen DJ, Tibboel D, Hamvas A, Carnielli VP. Surfactant metabolism in the neonate. Biol Neonate 2005: 87(4): 296-307. Cerca con Google

22. Schmitz G, Muller G. Structure and function of lamellar bodies, lipid-protein complexes involved in storage and secretion of cellular lipids. J Lipid Res 1991: 32(10): 1539-1570. Cerca con Google

23. Bohlin K, Merchak A, Spence K, Patterson BW, Hamvas A. Endogenous surfactant metabolism in newborn infants with and without respiratory failure. Pediatr Res 2003: 54(2): 185-191. Cerca con Google

24. Hall SB, Lu RZ, Venkitaraman AR, Hyde RW, Notter RH. Inhibition of pulmonary surfactant by oleic acid: mechanisms and characteristics. J Appl Physiol 1992: 72(5): 1708-1716. Cerca con Google

25. Schmidt R, Meier U, Yabut-Perez M, Walmrath D, Grimminger F, Seeger W, Gunther A. Alteration of fatty acid profiles in different pulmonary surfactant phospholipids in acute respiratory distress syndrome and severe pneumonia. Am J Respir Crit Care Med 2001: 163(1): 95-100. Cerca con Google

26. Jobe AH. Mechanisms to explain surfactant responses. Biol Neonate 2006: 89(4): 298-302. Cerca con Google

27. Bae CW, Takahashi A, Chida S, Sasaki M. Morphology and function of pulmonary surfactant inhibited by meconium. Pediatr Res 1998: 44(2): 187-191. Cerca con Google

28. Cayabyab RG, Kwong K, Jones C, Minoo P, Durand M. Lung inflammation and pulmonary function in infants with meconium aspiration syndrome. Pediatr Pulmonol 2007: 42(10): 898-905. Cerca con Google

CHAPTER 4 Cerca con Google

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13. Savani RC, Godinez RI, Godinez MH, Wentz E, Zaman A, Cui Z, Pooler PM, Guttentag SH, Beers MF, Gonzales LW, Ballard PL. Respiratory distress after intratracheal bleomycin: selective deficiency of surfactant proteins B and C. Am J Physiol Lung Cell Mol Physiol 2001: 281(3): L685-696. Cerca con Google

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15. Haczku A, Atochina EN, Tomer Y, Chen H, Scanlon ST, Russo S, Xu J, Panettieri RA, Jr., Beers MF. Aspergillus fumigatus-induced allergic airway inflammation alters surfactant homeostasis and lung function in BALB/c mice. Am J Respir Cell Mol Biol 2001: 25(1): 45-50. Cerca con Google

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18. Glasser SW, Burhans MS, Korfhagen TR, Na CL, Sly PD, Ross GF, Ikegami M, Whitsett JA. Altered stability of pulmonary surfactant in SP-C-deficient mice. Proc Natl Acad Sci U S A 2001: 98(11): 6366-6371. Cerca con Google

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