Abstract
The immunogenicity of hyaluronic acid was investigated. Rabbits were immunized with encapsulated group A and C streptococci. Intact long- chain hyaluronate was conjugated to BSA for use as antigen in an ELISA. Antibodies to the hyaluronate-BSA conjugate were detected in peak immune sera. The specificity of the antibodies for both mammalian and streptococcal hyaluronate was shown by inhibition studies. To further confirm the presence of antihyaluronate antibodies, hyaluronidase- digested streptococcal hyaluronate was conjugated to biotin and used as an antigen in the ELISA. A clear immunization effect was shown for each rabbit by the study of preimmune and postimmunization bleedings. Titers for each rabbit increased by greater than 32 - 256 - fold. Inhibition studies using hyaluronidase-digested hyaluronate and periodate-treated hyaluronate showed that the immunodominant site of antibody reactivity was a terminal glucuronic acid residue. Further studies showed that the carboxyl group of the terminal glucuronide was the major immunoreactive site. Both mammalian and streptococcal hyaluronate inhibited the immune rabbit sera reaction to streptococcal hyaluronate, demonstrating crossreactivity of these molecules. Thus, hyaluronate was shown to be immunogenic in rabbits.
Full Text
The Full Text of this article is available as a PDF (927.4 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- BITTER T., MUIR H. M. A modified uronic acid carbazole reaction. Anal Biochem. 1962 Oct;4:330–334. doi: 10.1016/0003-2697(62)90095-7. [DOI] [PubMed] [Google Scholar]
- Brandt J., Andersson L. O., Porath J. Covalent attachment of proteins to polysaccharide carriers by means of benzoquinone. Biochim Biophys Acta. 1975 Mar 28;386(1):196–202. doi: 10.1016/0005-2795(75)90259-7. [DOI] [PubMed] [Google Scholar]
- Braun D. G. The use of streptococcal antigens to probe the mechanisms of immunity. Microbiol Immunol. 1983;27(10):823–836. doi: 10.1111/j.1348-0421.1983.tb00647.x. [DOI] [PubMed] [Google Scholar]
- Cohen P. L., Rapoport R. G., Eisenberg R. A. Hidden autoantibodies against common serum proteins in murine systemic lupus erythematosus. Detection by in vitro plaque-forming cell assay. J Exp Med. 1985 Jun 1;161(6):1587–1592. doi: 10.1084/jem.161.6.1587. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Conrad G. W., Ager-Johnson P., Woo M. L. Antibodies against the predominant glycosaminoglycan of the mammalian cornea, keratan sulfate-I. J Biol Chem. 1982 Jan 10;257(1):464–471. [PubMed] [Google Scholar]
- Couchman J. R., Caterson B., Christner J. E., Baker J. R. Mapping by monoclonal antibody detection of glycosaminoglycans in connective tissues. Nature. 1984 Feb 16;307(5952):650–652. doi: 10.1038/307650a0. [DOI] [PubMed] [Google Scholar]
- Fillit H. M., Read S. E., Sherman R. L., Zabriskie J. B., Van de Rijn I. Cellular reactivity to altered glomerular basement membrane in glomerulonephritis. N Engl J Med. 1978 Apr 20;298(16):861–868. doi: 10.1056/NEJM197804202981601. [DOI] [PubMed] [Google Scholar]
- Fillit H., Damle S. P., Gregory J. D., Volin C., Poon-King T., Zabriskie J. Sera from patients with poststreptococcal glomerulonephritis contain antibodies to glomerular heparan sulfate proteoglycan. J Exp Med. 1985 Feb 1;161(2):277–289. doi: 10.1084/jem.161.2.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gotschlich E. C., Goldschneider I., Artenstein M. S. Human immunity to the meningococcus. IV. Immunogenicity of group A and group C meningococcal polysaccharides in human volunteers. J Exp Med. 1969 Jun 1;129(6):1367–1384. doi: 10.1084/jem.129.6.1367. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gotschlich E. C., Liu T. Y., Artenstein M. S. Human immunity to the meningococcus. 3. Preparation and immunochemical properties of the group A, group B, and group C meningococcal polysaccharides. J Exp Med. 1969 Jun 1;129(6):1349–1365. doi: 10.1084/jem.129.6.1349. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HIRSCH J. G., CHURCH A. B. Studies of phagocytosis of group A streptococci by polymorphonuclear leucocytes in vitro. J Exp Med. 1960 Mar 1;111:309–322. doi: 10.1084/jem.111.3.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hirst G. K. THE EFFECT OF A POLYSACCHARIDE-SPLITTING ENZYME ON STREPTOCOCCAL INFECTION. J Exp Med. 1941 Mar 31;73(4):493–506. doi: 10.1084/jem.73.4.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hofmann K., Finn F. M., Friesen H. J., Diaconescu C., Zahn H. Biotinylinsulins as potential tools for receptor studies. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2697–2700. doi: 10.1073/pnas.74.7.2697. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Humphrey J. H. Antigenic properties of hyaluronic acid. Biochem J. 1943 Oct;37(4):460–463. doi: 10.1042/bj0370460. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Inman J. K., Dintzis H. M. The derivatization of cross-linked polyacrylamide beads. Controlled introduction of functional groups for the preparation of special-purpose, biochemical adsorbents. Biochemistry. 1969 Oct;8(10):4074–4082. doi: 10.1021/bi00838a026. [DOI] [PubMed] [Google Scholar]
- Jenkins R. B., Hall T., Dorfman A. Chondroitin 6-sulfate oligosaccharides as immunological determinants of chick proteoglycans. J Biol Chem. 1981 Aug 25;256(16):8279–8282. [PubMed] [Google Scholar]
- Kefalides N. A., Pegg M. T., Ohno N., Poon-King T., Zabriskie J., Fillit H. Antibodies to basement membrane collagen and to laminin are present in sera from patients with poststreptococcal glomerulonephritis. J Exp Med. 1986 Mar 1;163(3):588–602. doi: 10.1084/jem.163.3.588. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kozel T. R., Gotschlich E. C. The capsule of cryptococcus neoformans passively inhibits phagocytosis of the yeast by macrophages. J Immunol. 1982 Oct;129(4):1675–1680. [PubMed] [Google Scholar]
- Nelles M. J., Niswander C. A., Karakawa W. W., Vann W. F., Arbeit R. D. Reactivity of type-specific monoclonal antibodies with Staphylococcus aureus clinical isolates and purified capsular polysaccharide. Infect Immun. 1985 Jul;49(1):14–18. doi: 10.1128/iai.49.1.14-18.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- QUINN R. W., SINGH K. P. Antigenicity of hyaluronic acid. Proc Soc Exp Biol Med. 1957 Jun;95(2):290–294. doi: 10.3181/00379727-95-23197. [DOI] [PubMed] [Google Scholar]
- RONDLE C. J., MORGAN W. T. The determination of glucosamine and galactosamine. Biochem J. 1955 Dec;61(4):586–589. doi: 10.1042/bj0610586. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sandson J., Hamerman D., Janis R., Rojkind M. Immunologic and chemical similarities between the streptococcus and human connective tissue. Trans Assoc Am Physicians. 1968;81:249–257. [PubMed] [Google Scholar]
- Seastone C. V. THE VIRULENCE OF GROUP C HEMOLYTIC STREPTOCOCCI OF ANIMAL ORIGIN. J Exp Med. 1939 Sep 30;70(4):361–378. doi: 10.1084/jem.70.4.361. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taylor R. L., Conrad H. E. Stoichiometric depolymerization of polyuronides and glycosaminoglycuronans to monosaccharides following reduction of their carbodiimide-activated carboxyl groups. Biochemistry. 1972 Apr 11;11(8):1383–1388. doi: 10.1021/bi00758a009. [DOI] [PubMed] [Google Scholar]
- Underhill C. B. Naturally-occurring antibodies which bind hyaluronate. Biochem Biophys Res Commun. 1982 Oct 29;108(4):1488–1494. doi: 10.1016/s0006-291x(82)80075-2. [DOI] [PubMed] [Google Scholar]
