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J Exp Med. Aug 1, 1976; 144(2): 428–443.
PMCID: PMC2190380

In vitro demonstration of a particular affinity of glomerular basement membrane and collagen for DNA. A possible basis for a local formation of DNA-anti-DNA complexes in systemic lupus erythematosus

Abstract

In vitro, collagen and collagen-like material in GBM, were demonstrated to have a particular high affinity for any DNA tested (mammalian, bacterial, viral, and plant). GBM fixed DNA 40-80 times more than HGG and BSA and 10-40 times more than bacterial LPS. GBM has a higher affinity for SSDNA than for DSDNA. This binding was inhibited at low pH, low ionic strength, and in the presence of anionic detergents, indicating that the highly negatively charged DNA may interact with the basic site on collagen or GBM by electrostatic forces. This interaction was competitively interfered with by DNA-binding proteins such as Clq. Complexes formed of DNA and anti-DNA antibodies did not exhibit the same binding property as free DNA. However, DNA which was already bound to GBM or to collagen could very efficiently bind anti-DNA antibodies and form immune complexes which would remain on these structures. The biological significance of the binding of DNA to GBM or to collagen should be particularly considered in relation to the pathogenesis of SLE. It is possible that DNA released from disrupted or degenerating cells would bind to surrounding collagen fibers or to basement membranes and then act as an immunoabsorbant for circulating anti-DNA antibodies. Some evidence for an in vivo binding of SSDNA to renal structures was obtained in mice treated with bacterial LPS 2 days before the injection of SSDNA.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Agnello V, Koffler D, Eisenberg JW, Winchester RJ, Kunkel HG. C1q PRECIPITINS IN THE SERA OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND OTHER HYPOCOMPLEMENTEMIC STATES: CHARACTERIZATION OF HIGH AND LOW MOLECULAR WEIGHT TYPES. J Exp Med. 1971 Sep 1;134(3):228–241. [PMC free article] [PubMed]
  • Harbeck RJ, Bardana EJ, Kohler PF, Carr RI. DNA:anti-DNA complexes: their detection in systemic lupus erythematosus sera. J Clin Invest. 1973 Apr;52(4):789–795. [PMC free article] [PubMed]
  • Nydegger UE, Lambert PH, Gerber H, Miescher PA. Circulating immune complexes in the serum in systemic lupus erythematosus and in carriers of hepatitis B antigen. Quantitation by binding to radiolabeled C1q. J Clin Invest. 1974 Aug;54(2):297–309. [PMC free article] [PubMed]
  • Zubler RH, Lange G, Lambert PH, Miescher PA. Detection of immune complexes in unheated sera by modified 125I-Clq binding test. Effect of heating on the binding of Clq by immune complexes and application of the test to systemic lupus erythematosus. J Immunol. 1976 Jan;116(1):232–235. [PubMed]
  • VAZQUEZ JJ, DIXON FJ. Immunohistochemical study of lesions in rheumatic fever, systemic lupus ervthematosus, and rheumatoid arthritis. Lab Invest. 1957 May-Jun;6(3):205–217. [PubMed]
  • Paronetto F, Koffler D. Immunofluorescent localization of immunoglobulins, complement, and fibrinogen in human diseases. I. Systemic lupus erythematosus. J Clin Invest. 1965 Oct;44(10):1657–1664. [PMC free article] [PubMed]
  • Tan EM, Kunkel HG. An immunofluorescent study of the skin lesions in systemic lupus erythematosus. Arthritis Rheum. 1966 Feb;9(1):37–46. [PubMed]
  • FARQUHAR MG, VERNIER RL, GOOD RA. An electron microscope study of the glomerulus in nephrosis, glomerulonephritis, and lupus erythematosus. J Exp Med. 1957 Nov 1;106(5):649–660. [PMC free article] [PubMed]
  • Grishman E, Churg J. Ultrastructure of dermal lesions in systemic lupus erythematosus. Lab Invest. 1970 Mar;22(3):189–197. [PubMed]
  • Tan EM, Schur PH, Carr RI, Kunkel HG. Deoxybonucleic acid (DNA) and antibodies to DNA in the serum of patients with systemic lupus erythematosus. J Clin Invest. 1966 Nov;45(11):1732–1740. [PMC free article] [PubMed]
  • Koffler D, Schur PH, Kunkel HG. Immunological studies concerning the nephritis of systemic lupus erythematosus. J Exp Med. 1967 Oct 1;126(4):607–624. [PMC free article] [PubMed]
  • Schur PH, Sandson J. Immunologic factors and clinical activity in systemic lupus erythematosus. N Engl J Med. 1968 Mar 7;278(10):533–538. [PubMed]
  • Krishnan C, Kaplan MH. Immunopathologic studies of systemic lupus erythematosus. II. Antinuclear reaction of gamma-globulin eluted from homogenates and isolated glomeruli of kidneys from patients with lupus nephritis. J Clin Invest. 1967 Apr;46(4):569–579. [PMC free article] [PubMed]
  • KLEMPERER P. The concept of collagen diseases. Am J Pathol. 1950 Jul;26(4):505–519. [PMC free article] [PubMed]
  • Yonemasu K, Stroud RM. Clq: rapid purification method for preparation of monospecific antisera and for biochemical studies. J Immunol. 1971 Feb;106(2):304–313. [PubMed]
  • Fournié GJ, Lambert PH, Meischer PA. Release of DNA in circulating blood and induction of anti-DNA antibodies after injection of bacterial lipopolysaccharides. J Exp Med. 1974 Nov 1;140(5):1189–1206. [PMC free article] [PubMed]
  • KRAKOWER CA, GREENSPON SA. Localization of the nephrotoxic antigen within the isolated renal glomerulus. AMA Arch Pathol. 1951 Jun;51(6):629–639. [PubMed]
  • LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed]
  • Commerford SL. Iodination of nucleic acids in vitro. Biochemistry. 1971 May 25;10(11):1993–2000. [PubMed]
  • McConahey PJ, Dixon FJ. A method of trace iodination of proteins for immunologic studies. Int Arch Allergy Appl Immunol. 1966;29(2):185–189. [PubMed]
  • BRAUDE AI, CAREY FJ, SUTHERLAND D, ZALESKY M. Studies with radioactive endotoxin. I. The use of Cr51 to label endotoxin of Escherichia coli. J Clin Invest. 1955 Jun;34(6):850–857. [PMC free article] [PubMed]
  • Creighton WD, Lambert PH, Miescher PA. Detection of antibodies and soluble antigen-antibody complexes by precipitation with polyethylene glycol. J Immunol. 1973 Oct;111(4):1219–1227. [PubMed]
  • FARR RS. A quantitative immunochemical measure of the primary interaction between I BSA and antibody. J Infect Dis. 1958 Nov-Dec;103(3):239–262. [PubMed]
  • Wold RT, Young FE, Tan EM, Farr RS. Deoxyribonucleic acid antibody: a method to detect its primary interaction with deoxyribonucleic acid. Science. 1968 Aug 23;161(3843):806–807. [PubMed]
  • STEELE WJ, BUSCH H. STUDIES ON ACIDIC NUCLEAR PROTEINS OF THE WALKER TUMOR AND LIVER. Cancer Res. 1963 Sep;23:1153–1163. [PubMed]
  • Kefalides NA. Isolation and characterization of the collagen from glomerular basement membrane. Biochemistry. 1968 Sep;7(9):3103–3112. [PubMed]
  • Yonemasu K, Stroud RM, Niedermeier W, Butler WT. Chemical studies of Clq; a modulator of immunoglobulin biology. Biochem Biophys Res Commun. 1971 Jun 18;43(6):1388–1394. [PubMed]
  • Knobel HR, Heusser C, Rodrick ML, Isliker H. Enzymatic digestion of the first component of human complement (C1q). J Immunol. 1974 Jun;112(6):2094–2101. [PubMed]
  • CRAMPTON CF, LIPSHITZ R, CHARGAFF E. Studies on nucleoproteins. II. Fractionation of deoxyribonucleic acids through fractional dissociation of their complexes with basic proteins. J Biol Chem. 1954 Nov;211(1):125–142. [PubMed]
  • SKARNES RC, WATSON DW. The inhibition of lysozyme by acidic polymers from pathogenic bacteria. J Bacteriol. 1955 Jul;70(1):110–112. [PMC free article] [PubMed]
  • Samaha RJ, Irvin WS. Deoxyribonucleic acid strandedness. Partial characterization of the antigenic regions binding antibodies in lupus erythematosus serum. J Clin Invest. 1975 Aug;56(2):446–457. [PMC free article] [PubMed]
  • Lambert PH, Dixon FJ. Pathogenesis of the glomerulonephritis of NZB/W mice. J Exp Med. 1968 Mar 1;127(3):507–522. [PMC free article] [PubMed]
  • Brentjens JR, Sepulveda M, Baliah T, Bentzel C, Erlanger BF, Elwood C, Montes M, Hsu KC, Andres GA. Interstitial immune complex nephritis in patients with systemic lupus erythematosus. Kidney Int. 1975 May;7(5):342–350. [PubMed]
  • Parker LP, Hahn BH, Osterland CK. Modification of NZB-NZW F1 autoimmune disease by development of tolerance to DNA. J Immunol. 1974 Jul;113(1):292–297. [PubMed]
  • Natali PG, Tan EM. Experimental renal disease induced by DNA-anti-DNA immune complexes. J Clin Invest. 1972 Feb;51(2):345–355. [PMC free article] [PubMed]
  • Koffler D, Agnello V, Winchester R, Kunkel HG. The occurrence of single-stranded DNA in the serum of patients with systemic lupus erythematosus and other diseases. J Clin Invest. 1973 Jan;52(1):198–204. [PMC free article] [PubMed]
  • Hughes GR, Cohen SA, Lightfoot RW, Jr, Meltzer JI, Christian CL. The release of DNA into serum and synovial fluid. Arthritis Rheum. 1971 Mar-Apr;14(2):259–266. [PubMed]
  • Kohler PF, Ten Bensel R. Serial complement component alterations in acute glomerulonephritis and systemic lupus erythematosus. Clin Exp Immunol. 1969 Feb;4(2):191–202. [PMC free article] [PubMed]
  • Hadjiyannaki K, Lachmann PJ. The relation of deoxyribonuclease inhibitor levels to the occurrence of antinuclear antibodies in NZB-NZW mice. Clin Exp Immunol. 1972 Jun;11(2):291–295. [PMC free article] [PubMed]

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