Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1979 Oct;64(4):1118–1129. doi: 10.1172/JCI109551

Serum concentration of human alpha 2 HS glycoprotein during the inflammatory process: evidence that alpha 2 HS glycoprotein is a negative acute-phase reactant.

J P Lebreton, F Joisel, J P Raoult, B Lannuzel, J P Rogez, G Humbert
PMCID: PMC372224  PMID: 90057

Abstract

A nonspecific opsonin function has been ascribed to human alpha 2 HS glycoprotein. Its serum level has been shown to be decreased in trauma patients. Recent studies from this laboratory revealed a heterogeneity among the products obtained in the course of the preparation of the protein. To date, no definitive agreement existed with regard to a molecular homogeneous entity of alpha 2 HS glycoprotein (Ba-alpha 2 glycoproteins). The purpose of the current work was to study the variations in serum level of alpha 2 HS in patients suffering from an acute inflammatory process of bacterial etiology and to determine whether a decrease in alpha 2 HS was accompanied by the appearance of fragments of this protein in the serum. A method of preparing alpha 2 HS was thus developed, using an immune absorbent as a final purification step. In an intermediary step of the preparation, alpha 2 HS was found to bind zinc when metal chelate affinity chromatography was employed. Immunologically and physico-chemically pure alpha 2 HS was obtained. The protein consists of a unique polypeptide chain of about 50,000 daltons and has a unique amino-terminal residue, alanine. However, the protein maintained its molecular integrity with difficulty, and spontaneous fragments ranging from 30,000 to less than 10,000 daltons were produced in some of the preparations. No major modification in the molecular structure of the protein was noted in the sera of subjects suffering from an acute inflammatory process. Serum level of alpha 2 HS and alpha 1 antitrypsin (AT)was determined in 23 patients. When the acute-phase (AP-)reactant alpha 1 AT was increased (difference with normal mean greater than +2 or +3 SD), the sera showed a large decrease in alpha 2 HS (difference with normal mean less than -2 or -3 SD). The serum level of alpha 2 HS, albumin, alpha 2 macroglobulin, and of positive AP-reactants, orosomucoidinal study of seven patients. The results were submitted to a principal components analysis. Alpha 2 HS showed a negative correlation with the AP-reactants alpha 1 AT, orosomucoid, and haptoglobin (P less than 0.05) and a positive correlation with albumin (P less than 0.05); these findings indicate that alpha 2 HS is a negative AP-reactant. In addition, analysis of the principal components confirms thestrong analogy between alpha 2 HS and albumin and indicates that serum level behavior of the AP-reactants during the course of the disease closely depends on the protein studied.

Full text

PDF
1118

Images in this article

Selected References

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

  1. Allen C., Saba T. M., Molnar J. Isolation, purification and characterization of opsonic protein. J Reticuloendothel Soc. 1973 May;13(5):410–423. [PubMed] [Google Scholar]
  2. Ashton B. A., Triffitt J. T., Herring G. M. Isolation and partial characterization of a glycoprotein from bovine cortical bone. Eur J Biochem. 1974 Jun 15;45(2):525–533. doi: 10.1111/j.1432-1033.1974.tb03577.x. [DOI] [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. BURGI W., SCHMID K. Preparation and properties of Zn-alpha 2-glycoprotein of normal human plasma. J Biol Chem. 1961 Apr;236:1066–1074. [PubMed] [Google Scholar]
  5. Blumenstock F. A., Saba T. M., Weber P. Purification of alpha-2-opsonic protein from human serum and its measurement by immunoassay. J Reticuloendothel Soc. 1978 Feb;23(2):119–134. [PubMed] [Google Scholar]
  6. Blumenstock F., Weber P., Saba T. M. Isolation and biochemical characterization of alpha-2-opsonic glycoprotein from rat serum. J Biol Chem. 1977 Oct 25;252(20):7156–7162. [PubMed] [Google Scholar]
  7. Dickson I. R., Poole A. R., Veis A. Localisation of plasma alpha2HS glycoprotein in mineralising human bone. Nature. 1975 Jul 31;256(5516):430–432. doi: 10.1038/256430a0. [DOI] [PubMed] [Google Scholar]
  8. GRAY W. R., HARTLEY B. S. THE STRUCTURE OF A CHYMOTRYPTIC PEPTIDE FROM PSEUDOMONAS CYTOCHROME C-551. Biochem J. 1963 Nov;89:379–380. doi: 10.1042/bj0890379. [DOI] [PubMed] [Google Scholar]
  9. Gros C., Labouesse B. Study of the dansylation reaction of amino acids, peptides and proteins. Eur J Biochem. 1969 Feb;7(4):463–470. doi: 10.1111/j.1432-1033.1969.tb19632.x. [DOI] [PubMed] [Google Scholar]
  10. HEIMBURGER N., HEIDE K., HAUPT H., SCHULTZE H. E. BAUSTEINANALYSEN VON HUMANSERUMPROTEINEN. Clin Chim Acta. 1964 Oct;10:293–307. doi: 10.1016/0009-8981(64)90059-2. [DOI] [PubMed] [Google Scholar]
  11. Hamberg U., Elg P., Nissinen E., Stelwagen P. Purification and heterogeneity of human kininogen. Use of DEAE-chromatography, molecular sieving and antibody specific immunosorbents. Int J Pept Protein Res. 1975;7(3):261–280. [PubMed] [Google Scholar]
  12. Jayle M. F., Engler R. Les différents profils des variations des protéines plasmatiques dans les états inflammatoires. Pathol Biol (Paris) 1974 Oct;22(8):645–650. [PubMed] [Google Scholar]
  13. Jeejeebhoy K. N., Ho J., Mehra R., Jeejeebhoy J., Bruce-Robertson A. Effects of hormones on the synthesis of alpha 1 (acute-phase) glycoprotein in isolated rat hepatocytes. Biochem J. 1977 Dec 15;168(3):347–352. doi: 10.1042/bj1680347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kushner I., Broder M. L., Karp D. Control of the acute phase response. Serum C-reactive protein kinetics after acute myocardial infarction. J Clin Invest. 1978 Feb;61(2):235–242. doi: 10.1172/JCI108932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Laurell C. B., Kullander S., Thorell J. Effect of administration of a combined estrogen-progestin contraceptive on the level of individual plasma proteins. Scand J Clin Lab Invest. 1968;21(4):337–343. doi: 10.3109/00365516809077003. [DOI] [PubMed] [Google Scholar]
  16. Lebreton J. P. Purification of the human plasma alpha2-SH glycoprotein by zinc chelate affinity chromatography. FEBS Lett. 1977 Aug 15;80(2):351–354. doi: 10.1016/0014-5793(77)80474-2. [DOI] [PubMed] [Google Scholar]
  17. Mancini G., Carbonara A. O., Heremans J. F. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry. 1965 Sep;2(3):235–254. doi: 10.1016/0019-2791(65)90004-2. [DOI] [PubMed] [Google Scholar]
  18. Neville D. M., Jr Molecular weight determination of protein-dodecyl sulfate complexes by gel electrophoresis in a discontinuous buffer system. J Biol Chem. 1971 Oct 25;246(20):6328–6334. [PubMed] [Google Scholar]
  19. OUCHTERLONY O. Diffusion-in-gel methods for immunological analysis. II. Prog Allergy. 1962;6:30–154. doi: 10.1159/000313795. [DOI] [PubMed] [Google Scholar]
  20. Roelcke D. Immunelektrophoretisch demonstrierbare Varianten des alpha-2-HS-glykoproteins. Spontane Modifikationen und ihre Induzierbarkeit. Z Gesamte Exp Med. 1968;148(3):243–254. [PubMed] [Google Scholar]
  21. SCHEIDEGGER J. J. Une micro-méthode de l'immuno-electrophorèse. Int Arch Allergy Appl Immunol. 1955;7(2):103–110. [PubMed] [Google Scholar]
  22. SCHMID K., BURGI W. Preparation and properties of the human plasma Ba-alpha2-glycoproteins. Biochim Biophys Acta. 1961 Mar 4;47:440–453. doi: 10.1016/0006-3002(61)90539-x. [DOI] [PubMed] [Google Scholar]
  23. Triffitt J. T., Gebauer U., Ashton B. A., Owen M. E., Reynolds J. J. Origin of plasma alpha2HS-glycoprotein and its accumulation in bone. Nature. 1976 Jul 15;262(5565):226–227. doi: 10.1038/262226a0. [DOI] [PubMed] [Google Scholar]
  24. Triffitt J. T., Owen M. Studies on bone matrix glycoproteins. Incorporation of (1-14C)glucosamine and plasma (14C)glycoprotein into rabbit cortical bone. Biochem J. 1973 Sep;136(1):125–134. doi: 10.1042/bj1360125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Triffitt J. T. Plasma proteins present in human cortical bone: enrichment of the alpha2HS-glycoprotein. Calcif Tissue Res. 1976 Nov 24;22(1):27–33. doi: 10.1007/BF02010343. [DOI] [PubMed] [Google Scholar]
  26. Webb K. S., Mickey D. D., Stone K. R., Paulson D. F. Correlation of apparent molecular weight and antigenicity of viral proteins: an SDS-page separation followed by acrylamide-agarose electrophoresis and immunoprecipitation. J Immunol Methods. 1977;14(3-4):343–353. doi: 10.1016/0022-1759(77)90145-4. [DOI] [PubMed] [Google Scholar]
  27. Weber K., Osborn M. The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. J Biol Chem. 1969 Aug 25;244(16):4406–4412. [PubMed] [Google Scholar]
  28. van Oss C. J., Bronson P. M., Border J. R. Changes in the serum alpha glycoprotein distribution in trauma patients. J Trauma. 1975 May;15(5):451–455. doi: 10.1097/00005373-197505000-00013. [DOI] [PubMed] [Google Scholar]
  29. van Oss C. J., Gillman C. F., Bronson P. M., Border J. R. Opsonic properties of human serum alpha-2 hs glycoprotein. Immunol Commun. 1974;3(4):329–335. doi: 10.3109/08820137409061113. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES