Abstract
Pulmozyme® recombinant human deoxyribonuclease I (DNase I) is currently used as a therapeutic for cystic fibrosis (CF) (1) and may be effective in the treatment of systemic lupus erythematosus (SLE) (2,3). As described in Chapter 20, degradation of high-molecular-weight DNA following inhalation of DNase I as an aerosol decreases the viscoelasticity of CF sputum and improves lung function. In SLE, antibodies to DNA and DNA/anti-DNA immune complexes have been implicated as the principal causative factor underlying clinical pathogenesis (4–7). Degradation of extracellular DNA or DNA/anti-DNA immune complexes may be of clinical benefit in SLE by two mechanisms. First, hydrolysis of the DNA component of membrane deposited DNA/anti-DNA immune complexes may reduce inflammation in the affected tissues. Second, hydrolysis of DNA and/or DNA/anti-DNA immune complexes in the circulation may elicit a decrease in the production of antibodies to DNA over time by reducing the antigen load (8).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ramsey, B. W. (1996) Management of pulmonary disease in patients with cystic fibrosis. New Engl. J. Med. 335, 179–188.
Lachmann, P. J. (1996) The in vivo destruction of antigen-a tool for probing and modulating an autoimmune response. Clin. Exp. Immunol. 106, 187–189.
Macanovic, M., Sinicropi, D., Shak, S., Baughman, S., Thiru, S., and Lachmann, P. J. (1996) The treatment of systemic lupus erythematosus (SLE) in NZB/W F1 hybrid mice; studies with recombinant murine DNase and with dexamethasone. Clin. Exp. Immunol. 106, 243–252.
Lefkowith, J. B. and Gilkeson, G. S. (1996) Nephritogenic autoantibodies in lupus: current concepts and continuing controversies. Arthritis Rheum. 39, 894–903.
Koffler, D., Agnello, V., and Kunkel, H. G. (1973) Polynucleotide immune complexes in serum and glomeruli of patients with systemic lupus erythematosus. Am. J. Pathol. 74, 109–124.
terBorg, E. J., Horst, G., Hummel, E. J., Limburg, P. C., and Kallenberg, C. G. M. (1990) Measurement of increases in anti-double-stranded DNA antibody levels as a predictor of disease exacerbation in systemic lupus erythematosus. Arthritis Rheum. 33, 634–643.
Yamada, A., Miyakawa, Y., and Kosaka, D. (1982) Entrapment of anti-DNA antibodies in the kidney of patients with systemic lupus erythematosus. Kidney Int. 22, 671–676.
Prince, W. S., Baker, D. L., Dodge, A. H., Ahmed, A. E., Chestnut, R. W., and Sinicropi, D. V. (1998) Pharmacodynamics of recombinant human DNase I in serum. Clin. Exp. Immunol. 113, 289–296.
Pan, C. Q., Dodge, A. H., Baker, D. L., Prince, W. S., Sinicropi, D. V., and Lazarus, R. A. (1998) Improved potency of hyperactive and actin-resistant human DNase I variants for treatment of cystic fibrosis and systemic lupus erythematosus. J. Biol. Chem. 273, 18,374–18,381.
Baron, W. F., Pan, C. Q., Spencer, S. A., Ryan, A. M., Lazarus, R. A., and Baker, K. P. (1998) Cloning and characterization of an actin-resistant DNase I-like endonuclease secreted by macrophages. Gene 215, 291–301.
Daugherty, A. L., Patapoff, T. W., Clark, R. C., Sinicropi, D. V., and Mrsny, R. J. (1995) Compaction assay: A rapid and simple in vitro method to assess the responsiveness of a biopolymer matrix to enzymatic modification. Biomaterials 16, 553–558.
Ulmer, J. S., Herzka, A., Toy, K. J., Baker, D. L., Dodge, A. H., Sinicropi, D., Shak, S., and Lazarus, R. A. (1996) Engineering actin-resistant human DNase I for treatment of cystic fibrosis. Proc. Natl. Acad. Sci USA 93, 8225–8229.
Macanovic, M. and Lachmann, P. J. (1997) Measurement of deoxyribonuclease I (DNase) in the serum and urine of systemic lupus erythematosus (SLE)-prone NZB/NZW mice by a new radial enzyme diffusion assay. Clin. Exp. Immunol. 108, 220–226.
Kissane, J. M. and Robins, E. (1958) The fluorometric measurement of deoxyribonucleic acid in animal tissues with special reference to the central nervous system. J. Biol. Chem. 233, 184–188.
Marquardt, D. W. (1963) An algorithm for least squares estimation of non linear parameters. J. Soc. Indust. Appl. Math. 11, 431–441.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2001 Humana Press Inc.
About this protocol
Cite this protocol
Sinicropi, D.V., Lazarus, R.A. (2001). Assays for Human DNase I Activity in Biological Matrices. In: Schein, C.H. (eds) Nuclease Methods and Protocols. Methods in Molecular Biology™, vol 160. Humana Press. https://doi.org/10.1385/1-59259-233-3:325
Download citation
DOI: https://doi.org/10.1385/1-59259-233-3:325
Publisher Name: Humana Press
Print ISBN: 978-0-89603-679-6
Online ISBN: 978-1-59259-233-3
eBook Packages: Springer Protocols