Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1976 Nov 2;144(5):1336–1346. doi: 10.1084/jem.144.5.1336

Connective tissue origin of the amyloid-related protein SAA

PMCID: PMC2190449  PMID: 792382

Abstract

Protein SAA is a serum protein related to the major constituent of secondary amyloid fibrils, protein AA, and has been suggested to be a precursor of the amyloid protein AA. In the present study, the origin of SAA was investigated by studying human fetal tissues and cultured human fetal fibroblasts with the indirect immunofluorescence technique. Anti-SAA antibodies reacted strongly with cultured fibroblasts producing a fine fibrillary cytoplasmic staining and with extracellular fibrils in loose connective tissues and vessel walls. The reactions were specifically inhibited by absorption with degraded amyloid material, isolated protein AA, isolated protein SAA, and sera from patients with elevated levels of SAA. In contrast, no inhibition was seen with amyloid fibril material devoid of AA protein or by human sera in which SAA was not detectable by double-diffusion tests. These observations showed that SAA-like material is produced by fibroblasts and indicate that it is a normal constituent of developing extracellular connective tissue fibers.

Full Text

The Full Text of this article is available as a PDF (2.4 MB).

Selected References

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

  1. Anders R. F., Natvig J. B., Michaelsen T. E., Husby G. Isolation and characterization of amyloid-related serum protein SAA as a low molecular weight protein. Scand J Immunol. 1975;4(4):397–401. doi: 10.1111/j.1365-3083.1975.tb02642.x. [DOI] [PubMed] [Google Scholar]
  2. Anders R. F., Nordstoga K., Natvig J. B., Husby G. Amyloid-related serum protein SAA in endotoxin-induced amyloidosis of the mink. J Exp Med. 1976 Mar 1;143(3):678–683. doi: 10.1084/jem.143.3.678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Avrameas S., Ternynck T. The cross-linking of proteins with glutaraldehyde and its use for the preparation of immunoadsorbents. Immunochemistry. 1969 Jan;6(1):53–66. doi: 10.1016/0019-2791(69)90178-5. [DOI] [PubMed] [Google Scholar]
  4. ChandraRajan J., Klein L. Purification and properties of an acidic protein from rat skin. J Biol Chem. 1975 Nov 10;250(21):8315–8320. [PubMed] [Google Scholar]
  5. Fullmer H. M. The histochemistry of the connective tissues. Int Rev Connect Tissue Res. 1965;3:1–76. doi: 10.1016/b978-1-4831-6753-4.50007-7. [DOI] [PubMed] [Google Scholar]
  6. Hance A. J., Crystal R. G. The connective tissue of lung. Am Rev Respir Dis. 1975 Nov;112(5):657–711. doi: 10.1164/arrd.1975.112.5.657. [DOI] [PubMed] [Google Scholar]
  7. Husby G., Natvig J. B. A serum component related to nonimmunoglobulin amyloid protein AS, a possible precursor of the fibrils. J Clin Invest. 1974 Apr;53(4):1054–1061. doi: 10.1172/JCI107642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Husby G., Natvig J. B., Sletten K., Nordstoga K., Anders R. F. An experimental model in mink for studying the relation between amyloid fibril protein AA and the related serum protein SAA. Scand J Immunol. 1975;4(8):811–816. doi: 10.1111/j.1365-3083.1975.tb03721.x. [DOI] [PubMed] [Google Scholar]
  9. Husby G., Sletten K., Michaelsen T. E., Natvig J. B. Alternative, non-immunoglobulin origin of amyloid fibrils. Nat New Biol. 1972 Aug 9;238(84):187–187. doi: 10.1038/newbio238187a0. [DOI] [PubMed] [Google Scholar]
  10. Janigan D. T. Experimental amyloidosis. Structural relationships of amyloid and reticulin in tissue sections and isolated preparations. Am J Pathol. 1966 Oct;49(4):657–678. [PMC free article] [PubMed] [Google Scholar]
  11. Levin M., Franklin E. C., Frangione B., Pras M. The amino acid sequence of a major nonimmunoglobulin component of some amyloid fibrils. J Clin Invest. 1972 Oct;51(10):2773–2776. doi: 10.1172/JCI107098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Levin M., Pras M., Franklin E. C. Immunologic studies of the major nonimmunoglobulin protein of amyloid. I. Identification and partial characterization of a related serum component. J Exp Med. 1973 Aug 1;138(2):373–380. doi: 10.1084/jem.138.2.373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Linder E. Differentiation of kidneys antigens in the human foetus. J Embryol Exp Morphol. 1969 Jun;21(3):517–537. [PubMed] [Google Scholar]
  14. Linder E., Vaheri A., Ruoslahti E., Wartiovaara J. Distribution of fibroblast surface antigen in the developing chick embryo. J Exp Med. 1975 Jul 1;142(1):41–49. doi: 10.1084/jem.142.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Linke R. P., Sipe J. D., Pollock P. S., Ignaczak T. F., Glenner G. G. Isolation of a low-molecular-weight serum component antigenically related to an amyloid fibril protein of unknown origin. Proc Natl Acad Sci U S A. 1975 Apr;72(4):1473–1476. doi: 10.1073/pnas.72.4.1473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Muir L. W., Bornstein P., Ross R. A presumptive subunit of elastic fiber microfibrils secreted by arterial smooth-muscle cells in culture. Eur J Biochem. 1976 Apr 15;64(1):105–114. doi: 10.1111/j.1432-1033.1976.tb10278.x. [DOI] [PubMed] [Google Scholar]
  17. Nordstoga K. Amyloidosis in mink induced by repeated injections of endotoxin. Acta Pathol Microbiol Scand A. 1972;80(2):159–168. doi: 10.1111/j.1699-0463.1972.tb02160.x. [DOI] [PubMed] [Google Scholar]
  18. Obrink B. The influence of glycosaminoglycans on the formation of fibers from monomeric tropocollagen in vitro. Eur J Biochem. 1973 Apr 2;34(1):129–137. doi: 10.1111/j.1432-1033.1973.tb02739.x. [DOI] [PubMed] [Google Scholar]
  19. Pras M., Johnson G. D., Holborow E. J., Glynn L. E. Antigenic properties of a non-collagenous reticulin component of normal connective tissue. Immunology. 1974 Sep;27(3):469–478. [PMC free article] [PubMed] [Google Scholar]
  20. Rizzetto M., Doniach D. Types of 'reticulin' antibodies detected in human sera by immunofluorescence. J Clin Pathol. 1973 Nov;26(11):841–851. doi: 10.1136/jcp.26.11.841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rosenthal C. J., Franklin E. C., Frangione B., Greenspan J. Isolation and partial characterization of SAA-an amyloid-related protein from human serum. J Immunol. 1976 May;116(5):1415–1418. [PubMed] [Google Scholar]
  22. Rosenthal C. J., Franklin E. C. Variation with age and disease of an amyloid A protein-related serum component. J Clin Invest. 1975 Apr;55(4):746–753. doi: 10.1172/JCI107985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rothbard S., Watson R. F. Demonstration of collagen in human tissues by immunofluorescence. Lab Invest. 1972 Jul;27(1):76–84. [PubMed] [Google Scholar]
  24. Vaheri A., Ruoslahti E., Linder E., Wartiovaara J., Keski-Oja J., Kuusela P., Saksela O. Fibroblast surface antigen (SF): molecular properties, distribution in vitro and in vivo, and altered expression in transformed cells. J Supramol Struct. 1976;4(1):63–70. doi: 10.1002/jss.400040107. [DOI] [PubMed] [Google Scholar]
  25. Wartiovaara J., Linder E., Ruoslahti E., Vaheri A. Distribution of fibroblast surface antigen: association with fibrillar structures of normal cells and loss upon viral transformation. J Exp Med. 1974 Dec 1;140(6):1522–1533. doi: 10.1084/jem.140.6.1522. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES