Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 4 November 1994:
Vol. 266. no. 5186, pp. 810 - 813
DOI: 10.1126/science.7973636
Prev | Table of Contents | Next

Articles

Science, Vol 266, Issue 5186, 810-813
Copyright © 1994 by American Association for the Advancement of Science

articles

Transformation of lupus-inducing drugs to cytotoxic products by activated neutrophils

X Jiang, G Khursigara, and RL Rubin

W. M. Keck Autoimmune Disease Center, Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037.

Drug-induced lupus is a serious side effect of certain medications, but the chemical features that confer this property and the underlying pathogenesis are puzzling. Prototypes of all six therapeutic classes of lupus-inducing drugs were highly cytotoxic only in the presence of activated neutrophils. Removal of extracellular hydrogen peroxide before, but not after, exposure of the drug to activated neutrophils prevented cytotoxicity. Neutrophil-dependent cytotoxicity required the enzymatic action of myeloperoxidase, resulting in the chemical transformation of the drug to a reactive product. The capacity of drugs to serve as myeloperoxidase substrates in vitro was associated with the ability to induce lupus in vivo.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Renal toxicity of therapeutic drugs.
R John and A M Herzenberg (2009)
J. Clin. Pathol. 62, 505-515
   Abstract »    Full Text »    PDF »
Hypotheses on the Etiology of Antineutrophil Cytoplasmic Autoantibody Associated Vasculitis: The Cause Is Hidden, but the Result Is Known.
R. A.F. de Lind van Wijngaarden, L. van Rijn, E. C. Hagen, R. A. Watts, G. Gregorini, J. W. C. Tervaert, A. D. Mahr, J. L. Niles, E. de Heer, J. A. Bruijn, et al. (2008)
Clin. J. Am. Soc. Nephrol. 3, 237-252
   Abstract »    Full Text »    PDF »
Pharmacogenetics, Drug-Metabolizing Enzymes, and Clinical Practice.
S. J. Gardiner and E. J. Begg (2006)
Pharmacol. Rev. 58, 521-590
   Abstract »    Full Text »    PDF »
Protein Adduct-Trapping by Hydrazinophthalazine Drugs: Mechanisms of Cytoprotection Against Acrolein-Mediated Toxicity.
P. C. Burcham, F. R. Fontaine, L. M. Kaminskas, D. R. Petersen, and S. M. Pyke (2004)
Mol. Pharmacol. 65, 655-664
   Abstract »    Full Text »    PDF »
Myeloperoxidase-antineutrophil cytoplasmic antibody-positive crescentic glomerulonephritis associated with benzylthiouracil therapy: report of the first case.
F. Jarraya, M. Abid, R. Jlidi, K. Mkaouar, M. Mnif, M. Kharrat, K. Charfeddine, K. Kammoun, M. Ben Hmida, and J. Hachicha (2003)
Nephrol. Dial. Transplant. 18, 2421-2423
   Full Text »    PDF »
An unusual case of ANCA positive disease.
S Delen, A Boonen, R Landewe, A A Kroon, S. van der Linden, and J W C. Tervaert (2003)
Ann Rheum Dis 62, 780-781
   Full Text »    PDF »
Prevalence of antineutrophil cytoplasmic autoantibodies in patients with tuberculosis.
L. F. Flores-Suarez, J. Cabiedes, A. R. Villa, F. J. van der Woude, and J. Alcocer-Varela (2003)
Rheumatology 42, 223-229
   Abstract »    Full Text »    PDF »
Risk Assessment of High-Energy Chemicals by in Vitro Toxicity Screening and Quantitative Structure-Activity Relationships.
S. Trohalaki, R. J. Zellmer, R. Pachter, S. M. Hussain, and J. M. Frazier (2002)
Toxicol. Sci. 68, 498-507
   Abstract »    Full Text »    PDF »
Case 21-2002 - A 21-Year-Old Man with Arthritis during Treatment for Hyperthyroidism.
S. M. Helfgott and R. N. Smith (2002)
N. Engl. J. Med. 347, 122-130
   Full Text »    PDF »
Minocycline-induced lupus: clinical features and response to rechallenge.
T. M. Lawson, N. Amos, D. Bulgen, and B. D. Williams (2001)
Rheumatology 40, 329-335
   Abstract »    Full Text »    PDF »
Diffuse Alveolar Hemorrhage and Pulmonary Capillaritis Due to Propylthiouracil.
S. S. Dhillon, D. Singh, N. Doe, A. M. Qadri, S. Ricciardi, and M. I. Schwarz (1999)
Chest 116, 1485-1488
   Abstract »    Full Text »    PDF »
Minocycline-induced lupus and autoimmune phenomena.
N. J. McHugh (1999)
Lupus 8, 417-418
   PDF »
Persistence of Autoreactive T Cell Drive Is Required to Elicit Anti-Chromatin Antibodies in a Murine Model of Drug-Induced Lupus.
A. Kretz-Rommel and R. L. Rubin (1999)
J. Immunol. 162, 813-820
   Abstract »    Full Text »    PDF »
Minocycline-induced Lupus in Adolescents.
E. Akin, L. C. Miller, and L. B. Tucker (1998)
Pediatrics 101, 926-928
   Full Text »    PDF »
Autocatalytic Processing of Heme by Lactoperoxidase Produces the Native Protein-bound Prosthetic Group.
G. D. DePillis, S.-i. Ozaki, J. M. Kuo, D. A. Maltby, and P. R.O. de Montellano (1997)
J. Biol. Chem. 272, 8857-8860
   Abstract »    Full Text »    PDF »
Lupus and Poly (ADP-Ribose).
S. Shall (1996)
Lupus 5, 1-3
   PDF »
Biochemical characterization of ADP-ribose polymer metabolism in SLE.
H-Y. Chen, R. Pertusi, J. Kirkland, B. Rubin, and E. Jacobson (1996)
Lupus 5, 14-21
   Abstract »    PDF »
Neutrophil activation during cardiopulmonary bypass in paediatric and adult patients.
D. F Larson, M. Bowers, and H W. Schechner (1996)
Perfusion 11, 21-27
   Abstract »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)