Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1988 Feb;130(2):261–267.

Circulating actin-gelsolin complexes following oleic acid-induced lung injury.

D B Smith 1, P A Janmey 1, S E Lind 1
PMCID: PMC1880527  PMID: 2829631

Abstract

Plasma gelsolin is one of two extracellular proteins that bind actin, a major body protein, with high affinity. The authors performed a series of experiments to determine whether tissue injury leads to actin release and the formation of circulating actin-gelsolin complexes. Two functions of plasma gelsolin, filament-nucleating and filament-severing activity, were used to measure total and free gelsolin concentrations, respectively. Both gelsolin and gelsolin-actin complexes nucleate actin assembly, whereas only free gelsolin severs actin filaments. Therefore, nucleation reflects the total gelsolin concentration, severing, the free gelsolin concentration, and the difference, gelsolin-actin complexes. Injection of F-actin in the rat caused a reduction in the free, but not total, gelsolin levels, consistent with the formation of circulating actin-gelsolin complexes. Oleic acid (50 mg/kg) administered intravenously in rats, a treatment that causes acute hemorrhagic pulmonary necrosis, caused the free gelsolin concentration to fall to a greater extent than the total gelsolin concentration, which indicated the presence of circulating actin-gelsolin complexes. Lower doses (9-27 mg/kg) in rabbits caused a qualitatively similar but smaller change in the free gelsolin level. Plasma gelsolin was immunoprecipitated at times when actin-gelsolin complexes were present, as determined functionally, and bound actin was demonstrated by immunoblotting with an anti-actin antiserum. These studies show that considerable amounts of actin are released into the extracellular space during acute lung injury and that circulating actin-gelsolin complexes can be detected in the peripheral blood.

Full text

PDF
263

Images in this article

265Figure 5
on p.265

Selected References

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

  1. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  2. Bryan J., Coluccio L. M. Kinetic analysis of F-actin depolymerization in the presence of platelet gelsolin and gelsolin-actin complexes. J Cell Biol. 1985 Oct;101(4):1236–1244. doi: 10.1083/jcb.101.4.1236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chaponnier C., Borgia R., Rungger-Brändle E., Weil R., Gabbiani G. An actin-destabilizing factor is present in human plasma. Experientia. 1979 Aug 15;35(8):1039–1041. doi: 10.1007/BF01949928. [DOI] [PubMed] [Google Scholar]
  4. Chaponnier C., Janmey P. A., Yin H. L. The actin filament-severing domain of plasma gelsolin. J Cell Biol. 1986 Oct;103(4):1473–1481. doi: 10.1083/jcb.103.4.1473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Coué M., Korn E. D. Interaction of plasma gelsolin with ADP-actin. J Biol Chem. 1986 Mar 15;261(8):3628–3631. [PubMed] [Google Scholar]
  6. De Scheerder I., Vandekerckhove J., Robbrecht J., Algoed L., De Buyzere M., De Langhe J., De Schrijver G., Clement D. Post-cardiac injury syndrome and an increased humoral immune response against the major contractile proteins (actin and myosin). Am J Cardiol. 1985 Oct 1;56(10):631–633. doi: 10.1016/0002-9149(85)91024-0. [DOI] [PubMed] [Google Scholar]
  7. Dickey B. F., Thrall R. S., McCormick J. R., Ward P. A. Oleic-acid-induced lung injury in the rat. Failure of indomethacin treatment or complement depletion to ablate lung injury. Am J Pathol. 1981 Jun;103(3):376–383. [PMC free article] [PubMed] [Google Scholar]
  8. Emerson D. L., Arnaud P., Galbraith R. M. Evidence of increased Gc:actin complexes in pregnant serum: a possible result of trophoblast embolism. Am J Reprod Immunol. 1983 Dec;4(4):185–189. doi: 10.1111/j.1600-0897.1983.tb00276.x. [DOI] [PubMed] [Google Scholar]
  9. Gabbiani G., Ryan G. B., Lamelin J. P., Vassalli P., Majno G., Bouvier C. A., Cruchaud A., Lüscher E. F. Human smooth muscle autoantibody. Its identification as antiactin antibody and a study of its binding to "nonmuscular" cells. Am J Pathol. 1973 Sep;72(3):473–488. [PMC free article] [PubMed] [Google Scholar]
  10. Haddad J. G. Human serum binding protein for vitamin D and its metabolites (DBP): evidence that actin is the DBP binding component in human skeletal muscle. Arch Biochem Biophys. 1982 Feb;213(2):538–544. doi: 10.1016/0003-9861(82)90581-1. [DOI] [PubMed] [Google Scholar]
  11. Harper K. D., McLeod J. F., Kowalski M. A., Haddad J. G. Vitamin D binding protein sequesters monomeric actin in the circulation of the rat. J Clin Invest. 1987 May;79(5):1365–1370. doi: 10.1172/JCI112963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Harris H. E., Bamburg J. R., Weeds A. G. Actin filament disassembly in blood plasma. FEBS Lett. 1980 Nov 17;121(1):175–177. doi: 10.1016/0014-5793(80)81291-9. [DOI] [PubMed] [Google Scholar]
  13. Janmey P. A., Chaponnier C., Lind S. E., Zaner K. S., Stossel T. P., Yin H. L. Interactions of gelsolin and gelsolin-actin complexes with actin. Effects of calcium on actin nucleation, filament severing, and end blocking. Biochemistry. 1985 Jul 2;24(14):3714–3723. doi: 10.1021/bi00335a046. [DOI] [PubMed] [Google Scholar]
  14. Janmey P. A., Lind S. E. Capacity of human serum to depolymerize actin filaments. Blood. 1987 Aug;70(2):524–530. [PubMed] [Google Scholar]
  15. Janmey P. A., Lind S. E., Yin H. L., Stossel T. P. Effects of semi-dilute actin solutions on the mobility of fibrin protofibrils during clot formation. Biochim Biophys Acta. 1985 Aug 16;841(2):151–158. doi: 10.1016/0304-4165(85)90016-9. [DOI] [PubMed] [Google Scholar]
  16. Janmey P. A., Stossel T. P. Kinetics of actin monomer exchange at the slow growing ends of actin filaments and their relation to the elongation of filaments shortened by gelsolin. J Muscle Res Cell Motil. 1986 Oct;7(5):446–454. doi: 10.1007/BF01753587. [DOI] [PubMed] [Google Scholar]
  17. Janmey P. A., Stossel T. P., Lind S. E. Sequential binding of actin monomers to plasma gelsolin and its inhibition by vitamin D-binding protein. Biochem Biophys Res Commun. 1986 Apr 14;136(1):72–79. doi: 10.1016/0006-291x(86)90878-8. [DOI] [PubMed] [Google Scholar]
  18. Kurth M. C., Wang L. L., Dingus J., Bryan J. Purification and characterization of a gelsolin-actin complex from human platelets. Evidence for Ca2+-insensitive functions. J Biol Chem. 1983 Sep 25;258(18):10895–10903. [PubMed] [Google Scholar]
  19. Kwiatkowski D. J., Stossel T. P., Orkin S. H., Mole J. E., Colten H. R., Yin H. L. Plasma and cytoplasmic gelsolins are encoded by a single gene and contain a duplicated actin-binding domain. Nature. 1986 Oct 2;323(6087):455–458. doi: 10.1038/323455a0. [DOI] [PubMed] [Google Scholar]
  20. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  21. Lee W. M., Emerson D. L., Werner P. A., Arnaud P., Goldschmidt-Clermont P., Galbraith R. M. Decreased serum group-specific component protein levels and complexes with actin in fulminant hepatic necrosis. Hepatology. 1985 Mar-Apr;5(2):271–275. doi: 10.1002/hep.1840050220. [DOI] [PubMed] [Google Scholar]
  22. Lees A., Haddad J. G., Lin S. Brevin and vitamin D binding protein: comparison of the effects of two serum proteins on actin assembly and disassembly. Biochemistry. 1984 Jun 19;23(13):3038–3047. doi: 10.1021/bi00308a030. [DOI] [PubMed] [Google Scholar]
  23. Lidman K., Biberfeld G., Fagraeus A., Norberg R., Torstensson R., Utter G., Carlsson L., Luca J., Lindberg U. Anti-actin specificity of human smooth muscle antibodies in chronic active hepatitis. Clin Exp Immunol. 1976 May;24(2):266–272. [PMC free article] [PubMed] [Google Scholar]
  24. Lind S. E., Janmey P. A., Chaponnier C., Herbert T. J., Stossel T. P. Reversible binding of actin to gelsolin and profilin in human platelet extracts. J Cell Biol. 1987 Aug;105(2):833–842. doi: 10.1083/jcb.105.2.833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lind S. E., Smith D. B., Janmey P. A., Stossel T. P. Role of plasma gelsolin and the vitamin D-binding protein in clearing actin from the circulation. J Clin Invest. 1986 Sep;78(3):736–742. doi: 10.1172/JCI112634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Norberg R., Thorstensson R., Utter G., Fagraeus A. F-Actin-depolymerizing activity of human serum. Eur J Biochem. 1979 Oct 15;100(2):575–583. doi: 10.1111/j.1432-1033.1979.tb04204.x. [DOI] [PubMed] [Google Scholar]
  27. Smith D. B., Janmey P. A., Herbert T. J., Lind S. E. Quantitative measurement of plasma gelsolin and its incorporation into fibrin clots. J Lab Clin Med. 1987 Aug;110(2):189–195. [PubMed] [Google Scholar]
  28. Spudich J. A., Watt S. The regulation of rabbit skeletal muscle contraction. I. Biochemical studies of the interaction of the tropomyosin-troponin complex with actin and the proteolytic fragments of myosin. J Biol Chem. 1971 Aug 10;246(15):4866–4871. [PubMed] [Google Scholar]
  29. Stossel T. P. Contractile proteins in cell structure and function. Annu Rev Med. 1978;29:427–457. doi: 10.1146/annurev.me.29.020178.002235. [DOI] [PubMed] [Google Scholar]
  30. Thorstensson R., Utter G., Norberg R. Further characterization of the Ca2+-dependent F-actin-depolymerizing protein of human serum. Eur J Biochem. 1982 Aug;126(1):11–16. doi: 10.1111/j.1432-1033.1982.tb06738.x. [DOI] [PubMed] [Google Scholar]
  31. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Van Baelen H., Bouillon R., De Moor P. Vitamin D-binding protein (Gc-globulin) binds actin. J Biol Chem. 1980 Mar 25;255(6):2270–2272. [PubMed] [Google Scholar]
  33. Walsh P. G., Haddad J. G. "Rocket" immunoelectrophoresis assay of vitamin D-binding protein (Gc globulin) in human serum. Clin Chem. 1982 Aug;28(8):1781–1783. [PubMed] [Google Scholar]
  34. Yin H. L., Kwiatkowski D. J., Mole J. E., Cole F. S. Structure and biosynthesis of cytoplasmic and secreted variants of gelsolin. J Biol Chem. 1984 Apr 25;259(8):5271–5276. [PubMed] [Google Scholar]
  35. Yin H. L., Stossel T. P. Control of cytoplasmic actin gel-sol transformation by gelsolin, a calcium-dependent regulatory protein. Nature. 1979 Oct 18;281(5732):583–586. doi: 10.1038/281583a0. [DOI] [PubMed] [Google Scholar]
  36. Young W. O., Goldschmidt-Clermont P. J., Emerson D. L., Lee W. M., Jollow D. J., Galbraith R. M. Correlation between extent of liver damage in fulminant hepatic necrosis and complexing of circulating group-specific component (vitamin D-binding protein). J Lab Clin Med. 1987 Jul;110(1):83–90. [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES