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. 1989 Jun;134(6):1285–1293.

Expression of the 35kDa and low molecular weight surfactant-associated proteins in the lungs of infants dying with respiratory distress syndrome.

D E deMello 1, D S Phelps 1, G Patel 1, J Floros 1, D Lagunoff 1
PMCID: PMC1879954  PMID: 2757118

Abstract

Newborn respiratory distress syndrome (RDS) results from a deficiency of pulmonary surfactant. Surfactant has three ultrastructural forms: lamellar bodies, which, when secreted from Type II pneumocytes, transform into tubular myelin; tubular myelin in turn gives rise to the phospholipid monolayer at the air-fluid interface in the alveolus that constitutes functional surfactant. It has been shown previously that the lungs of infants dying from RDS lacked tubular myelin despite the presence of abundant lamellar bodies, whereas the lungs of control infants dying from other causes had both tubular myelin and lamellar bodies. An abnormality in the conversion of lamellar bodies to tubular myelin in RDS was proposed as a possible explanation for this finding. To evaluate the role of surfactant proteins (SPs) in this conversion, the authors re-examined the lungs of 11 RDS infants and 10 control infants for reactivity with antisera to high and low molecular weight SPs. In control infants, abundant intense staining with antisera to both types of SPs was found, but in the RDS lungs, staining was weaker than that in controls and less intense for high molecular weight compared to low molecular weight SPs. In lungs from patients with RDS, although staining increased with increasing gestational and post-natal ages, the intensity was less than control levels at all ages. The correlation of deficiency of SPs in RDS with lack of tubular myelin suggests that SPs may be involved in the conversion of normal lamellar bodies to tubular myelin and that the deficiency of SPs could explain the persistent respiratory distress in the presence of surfactant phospholipid synthesis.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AVERY M. E., MEAD J. Surface properties in relation to atelectasis and hyaline membrane disease. AMA J Dis Child. 1959 May;97(5 Pt 1):517–523. doi: 10.1001/archpedi.1959.02070010519001. [DOI] [PubMed] [Google Scholar]
  2. Balis J. U., Paterson J. F., Paciga J. E., Haller E. M., Shelley S. A. Distribution and subcellular localization of surfactant-associated glycoproteins in human lung. Lab Invest. 1985 Jun;52(6):657–669. [PubMed] [Google Scholar]
  3. Beckmann H. J., Dierichs R. Extramembraneous particles and structural variations of tubular myelin figures in rat lung surfactant. J Ultrastruct Res. 1984 Jan;86(1):57–66. doi: 10.1016/s0022-5320(84)90095-9. [DOI] [PubMed] [Google Scholar]
  4. Benson B. J., Hawgood S., Williams M. C. Role of apoprotein and calcium ions in surfactant function. Exp Lung Res. 1984;6(3-4):223–236. doi: 10.3109/01902148409109250. [DOI] [PubMed] [Google Scholar]
  5. Benson B. J., Williams M. C., Sueishi K., Goerke J., Sargeant T. Role of calcium ions the structure and function of pulmonary surfactant. Biochim Biophys Acta. 1984 Mar 27;793(1):18–27. doi: 10.1016/0005-2760(84)90048-1. [DOI] [PubMed] [Google Scholar]
  6. Chi E. Y., Lagunoff D. Linear arrays of intramembranous particles in pulmonary tubular myelin. Proc Natl Acad Sci U S A. 1978 Dec;75(12):6225–6229. doi: 10.1073/pnas.75.12.6225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Coalson J. J., Winter V. T., Martin H. M., King R. J. Colloidal gold immunoultrastructural localization of rat surfactant. Am Rev Respir Dis. 1986 Feb;133(2):230–237. doi: 10.1164/arrd.1986.133.2.230. [DOI] [PubMed] [Google Scholar]
  8. Efrati H., Hawgood S., Williams M. C., Hong K., Benson B. J. Divalent cation and hydrogen ion effects on the structure and surface activity of pulmonary surfactant. Biochemistry. 1987 Dec 1;26(24):7986–7993. doi: 10.1021/bi00398a066. [DOI] [PubMed] [Google Scholar]
  9. Floros J., Phelps D. S., Taeusch H. W. Biosynthesis and in vitro translation of the major surfactant-associated protein from human lung. J Biol Chem. 1985 Jan 10;260(1):495–500. [PubMed] [Google Scholar]
  10. Floros J., Steinbrink R., Jacobs K., Phelps D., Kriz R., Recny M., Sultzman L., Jones S., Taeusch H. W., Frank H. A. Isolation and characterization of cDNA clones for the 35-kDa pulmonary surfactant-associated protein. J Biol Chem. 1986 Jul 5;261(19):9029–9033. [PubMed] [Google Scholar]
  11. Gil J., Reiss O. K. Isolation and characterization of lamellar bodies and tubular myelin from rat lung homogenates. J Cell Biol. 1973 Jul;58(1):152–171. doi: 10.1083/jcb.58.1.152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Groniowski J. A. Fine structural basis of pulmonary surfactant. Int Rev Exp Pathol. 1983;25:183–238. [PubMed] [Google Scholar]
  13. Groniowski J. Presumable role of surface glycoprotein of alveolar pneumonocytes in transformation of lamellar bodies into tubular myelin. Acta Med Pol. 1979;20(4):393–396. [PubMed] [Google Scholar]
  14. Groniowski J., Walski M. Further studies on the tubular myelin structure of extracellular alveolar lining layer. Acta Med Pol. 1979;20(1):15–16. [PubMed] [Google Scholar]
  15. Hook G. E., Gilmore L. B., Talley F. A. Dissolution and reassembly of tubular myelin-like multilamellated structures from the lungs of patients with pulmonary alveolar proteinosis. Lab Invest. 1986 Aug;55(2):194–208. [PubMed] [Google Scholar]
  16. Jacobs K. A., Phelps D. S., Steinbrink R., Fisch J., Kriz R., Mitsock L., Dougherty J. P., Taeusch H. W., Floros J. Isolation of a cDNA clone encoding a high molecular weight precursor to a 6-kDa pulmonary surfactant-associated protein. J Biol Chem. 1987 Jul 15;262(20):9808–9811. [PubMed] [Google Scholar]
  17. Katyal S. L., Amenta J. S., Singh G., Silverman J. A. Deficient lung surfactant apoproteins in amniotic fluid with mature phospholipid profile from diabetic pregnancies. Am J Obstet Gynecol. 1984 Jan 1;148(1):48–53. doi: 10.1016/s0002-9378(84)80031-9. [DOI] [PubMed] [Google Scholar]
  18. Kikkawa Y., Manabe T. The freeze-fracture study of alveolar type II cells and alveolar content in fetal rabbit lung. Anat Rec. 1978 Mar;190(3):627–637. doi: 10.1002/ar.1091900302. [DOI] [PubMed] [Google Scholar]
  19. Kikkawa Y. Morphology of alveolar lining layer. Anat Rec. 1970 Aug;167(4):389–400. doi: 10.1002/ar.1091670403. [DOI] [PubMed] [Google Scholar]
  20. King R. J. The surfactant system of the lung. Fed Proc. 1974 Nov;33(11):2238–2247. [PubMed] [Google Scholar]
  21. Kobayashi T., Robertson B. Surface adsorption of pulmonary surfactant in relation to bulk-phase concentration and presence of CaCl2. Respiration. 1983;44(1):63–70. doi: 10.1159/000194529. [DOI] [PubMed] [Google Scholar]
  22. Kuroki Y., Dempo K., Akino T. Immunohistochemical study of human pulmonary surfactant apoproteins with monoclonal antibodies. Pathologic application for hyaline membrane disease. Am J Pathol. 1986 Jul;124(1):25–33. [PMC free article] [PubMed] [Google Scholar]
  23. Kuroki Y., Takahashi H., Fukada Y., Mikawa M., Inagawa A., Fujimoto S., Akino T. Two-site "simultaneous" immunoassay with monoclonal antibodies for the determination of surfactant apoproteins in human amniotic fluid. Pediatr Res. 1985 Oct;19(10):1017–1020. doi: 10.1203/00006450-198510000-00013. [DOI] [PubMed] [Google Scholar]
  24. Liley H. G., Hawgood S., Wellenstein G. A., Benson B., White R. T., Ballard P. L. Surfactant protein of molecular weight 28,000-36,000 in cultured human fetal lung: cellular localization and effect of dexamethasone. Mol Endocrinol. 1987 Mar;1(3):205–215. doi: 10.1210/mend-1-3-205. [DOI] [PubMed] [Google Scholar]
  25. Notter R. H., Finkelstein J. N., Taubold R. D. Comparative adsorption of natural lung surfactant, extracted phospholipids, and artificial phospholipid mixtures to the air-water interface. Chem Phys Lipids. 1983 Jul;33(1):67–80. doi: 10.1016/0009-3084(83)90009-9. [DOI] [PubMed] [Google Scholar]
  26. Notter R. H., Shapiro D. L., Ohning B., Whitsett J. A. Biophysical activity of synthetic phospholipids combined with purified lung surfactant 6000 dalton apoprotein. Chem Phys Lipids. 1987 Jun;44(1):1–17. doi: 10.1016/0009-3084(87)90002-8. [DOI] [PubMed] [Google Scholar]
  27. Paul G. W., Hassett R. J., Reiss O. K. Formation of lung surfactant films from intact lamellar bodies. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3617–3620. doi: 10.1073/pnas.74.8.3617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Phelps D. S., Floros J. Localization of surfactant protein synthesis in human lung by in situ hybridization. Am Rev Respir Dis. 1988 Apr;137(4):939–942. doi: 10.1164/ajrccm/137.4.939. [DOI] [PubMed] [Google Scholar]
  29. Phelps D. S., Harding H. P. Immunohistochemical localization of a low molecular weight surfactant-associated protein in human lung. J Histochem Cytochem. 1987 Nov;35(11):1339–1342. doi: 10.1177/35.11.3309049. [DOI] [PubMed] [Google Scholar]
  30. Phelps D. S., Smith L. M., Taeusch H. W. Characterization and partial amino acid sequence of a low molecular weight surfactant protein. Am Rev Respir Dis. 1987 May;135(5):1112–1117. doi: 10.1164/arrd.1987.135.5.1112. [DOI] [PubMed] [Google Scholar]
  31. Phelps D. S., Taeusch H. W., Jr, Benson B., Hawgood S. An electrophoretic and immunochemical characterization of human surfactant-associated proteins. Biochim Biophys Acta. 1984 Dec 7;791(2):226–238. doi: 10.1016/0167-4838(84)90013-x. [DOI] [PubMed] [Google Scholar]
  32. Possmayer F. A proposed nomenclature for pulmonary surfactant-associated proteins. Am Rev Respir Dis. 1988 Oct;138(4):990–998. doi: 10.1164/ajrccm/138.4.990. [DOI] [PubMed] [Google Scholar]
  33. Reid L. M. Lung growth in health and disease. Br J Dis Chest. 1984 Apr;78(2):113–134. [PubMed] [Google Scholar]
  34. Sanders R. L., Hassett R. J., Vatter A. E. Isolation of lung lamellar bodies and their conversion to tubular myelin figures in vitro. Anat Rec. 1980 Nov;198(3):485–501. doi: 10.1002/ar.1091980310. [DOI] [PubMed] [Google Scholar]
  35. Sanderson R. J., Vatter A. E. A mode of formation of tubular myelin from lamellar bodies in the lung. J Cell Biol. 1977 Sep;74(3):1027–1031. doi: 10.1083/jcb.74.3.1027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Shelley S. A., Balis J. U., Paciga J. E., Knuppel R. A., Ruffolo E. H., Bouis P. J., Jr Surfactant "apoproteins" in human amniotic fluid: an enzyme-linked immunosorbent assay for the prenatal assessment of lung maturity. Am J Obstet Gynecol. 1982 Sep 15;144(2):224–228. doi: 10.1016/0002-9378(82)90632-9. [DOI] [PubMed] [Google Scholar]
  37. Sorokin S P. A morphologic and cytochemical study on the great alveolar cell. J Histochem Cytochem. 1966 Dec;14(12):884–897. doi: 10.1177/14.12.884. [DOI] [PubMed] [Google Scholar]
  38. Stahlman M. T. Newborn intensive care: Success or failure? J Pediatr. 1984 Jul;105(1):162–167. doi: 10.1016/s0022-3476(84)80386-8. [DOI] [PubMed] [Google Scholar]
  39. Weibel E. R., Gil J. Electron microscopic demonstration of an extracellular duplex lining layer of alveoli. Respir Physiol. 1968 Jan;4(1):42–57. doi: 10.1016/0034-5687(68)90006-6. [DOI] [PubMed] [Google Scholar]
  40. Weibel E. R., Kistler G. S., Töndury G. A stereologic electron microscope study of "tubular myelin figures" in alveolar fluids of rat lungs. Z Zellforsch Mikrosk Anat. 1966;69:418–427. doi: 10.1007/BF00406293. [DOI] [PubMed] [Google Scholar]
  41. Whitsett J. A., Ohning B. L., Ross G., Meuth J., Weaver T., Holm B. A., Shapiro D. L., Notter R. H. Hydrophobic surfactant-associated protein in whole lung surfactant and its importance for biophysical activity in lung surfactant extracts used for replacement therapy. Pediatr Res. 1986 May;20(5):460–467. doi: 10.1203/00006450-198605000-00016. [DOI] [PubMed] [Google Scholar]
  42. Whitsett J. A., Weaver T. E., Clark J. C., Sawtell N., Glasser S. W., Korfhagen T. R., Hull W. M. Glucocorticoid enhances surfactant proteolipid Phe and pVal synthesis and RNA in fetal lung. J Biol Chem. 1987 Nov 15;262(32):15618–15623. [PubMed] [Google Scholar]
  43. Williams M. C. Conversion of lamellar body membranes into tubular myelin in alveoli of fetal rat lungs. J Cell Biol. 1977 Feb;72(2):260–277. doi: 10.1083/jcb.72.2.260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Williams M. C. Ultrastructure of tubular myelin and lamellar bodies in fast-frozen adult rat lung. Exp Lung Res. 1982 Dec;4(1):37–46. doi: 10.3109/01902148209039248. [DOI] [PubMed] [Google Scholar]
  45. Yu S. H., Possmayer F. Reconstitution of surfactant activity by using the 6 kDa apoprotein associated with pulmonary surfactant. Biochem J. 1986 May 15;236(1):85–89. doi: 10.1042/bj2360085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. deMello D. E., Chi E. Y., Doo E., Lagunoff D. Absence of tubular myelin in lungs of infants dying with hyaline membrane disease. Am J Pathol. 1987 Apr;127(1):131–139. [PMC free article] [PubMed] [Google Scholar]

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