Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1976 Oct;58(4):871–879. doi: 10.1172/JCI108540

The effect of D-penicillamine on polymorphonuclear leukocyte function.

H Chwalinska-Sadowska, J Baum
PMCID: PMC333250  PMID: 965493

Abstract

D-Penicillamine, a reducing and chelating agent used in the treating of rheumatoid arthritis, was tested for its effects of polymorphonuclear leukocyte chemotaxis, phagocytosis, and lysosomal enzymes. beta-Glucuronidase release from polymorphonuclear leukocytes after phagocytosis of latex particles was not affected by D-penicillamine at concentrations ranging from 25 to 400 mg/liter. No direct effect was seen on enzyme activity at the maximum concentration of the drug. There was no inhibition of latex particle ingestion. No cell damage was found at 400 mg/liter penicillamine as measured by lactic dehydrogenase release. At this drug concentration there was only a 15% reduction in hemolytic complement levels. Chemotaxis was significantly decreased at concentrations of 50 mg/liter with a dose-dependent effect at higher concentrations which showed a plateau from 200 to 400 mg/liter. The parent compound D-cysteine was also tested in these systems. The same lack of effect of phagocytosis and enzyme release was found. D-Cysteine did inhibit chemotaxis but to a lesser degree than D-penicillamine. This dicotomy of drug effect may indicate that the beneficial action of D-penicillamine in the treatment of rheumatoid arthritis is due to the decreased chemotaxis of polymorphonuclear leukocytes into the joint, while the absence of an effect of phagocytosis and lysosomal enzymes shows the cells can still function to ingest and destroy bacteria. This latter effect correlates with the absence of infection in patients treated with this compound.

Full text

PDF
879

Selected References

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

  1. Austen K. F. Inborn and acquired abnormalities of the complement system of man. Johns Hopkins Med J. 1971 Feb;128(2):57–74. [PubMed] [Google Scholar]
  2. Baum J., Mowat A. G., Kirk J. A. A simplified method for the measurement of chemotaxis of polymorphonuclear leukocytes from human blood. J Lab Clin Med. 1971 Mar;77(3):501–509. [PubMed] [Google Scholar]
  3. Berenberg J. L., Ward P. A. Chemotactic factor inactivator in normal human serum. J Clin Invest. 1973 May;52(5):1200–1206. doi: 10.1172/JCI107287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bluestone R., Goldberg L. S. Effect of D-penicillamine on serum immunoglobulins and rheumatoid factor. Ann Rheum Dis. 1973 Jan;32(1):50–52. doi: 10.1136/ard.32.1.50. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brandt L., Svensson B. Letter: Effect of penicillamine on peripheral-blood lymphocytes in rheumatoid arthritis. Lancet. 1975 Feb 15;1(7903):394–395. doi: 10.1016/s0140-6736(75)91309-4. [DOI] [PubMed] [Google Scholar]
  6. Dabrowska B. K., Ryzewski J., Dabrowski M. P., Ryzewska A. G. Suppression of MLC-reactivity of rat lymphocytes by L-cysteine hydrochloride. Bull Acad Pol Sci Biol. 1974;22(5):287–291. [PubMed] [Google Scholar]
  7. Day A. T., Golding J. R., Lee P. N., Butterworth A. D. Penicillamine in rheumatoid disease: a long-term study. Br Med J. 1974 Feb 2;1(5900):180–183. doi: 10.1136/bmj.1.5900.180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hawkins D. Neutrophilic leukocytes in immunologic reactions in vitro. 3. Pharmacologic modulation of lysosomal constituent release. Clin Immunol Immunopathol. 1974 Jan;2(2):141–152. doi: 10.1016/0090-1229(74)90034-8. [DOI] [PubMed] [Google Scholar]
  9. Hawkins D., Peeters S. The response of polymorphonuclear leukocytes to immune complexes in vitro. Lab Invest. 1971 Jun;24(6):483–491. [PubMed] [Google Scholar]
  10. Huskisson E. C., Berry H. Some immunological changes in rheumatoid arthritis among patients receiving penicillamine and gold. Postgrad Med J. 1974 Aug;50 (Suppl 2):59–61. [PubMed] [Google Scholar]
  11. Ignarro L. J., Lint T. F., George W. J. Hormonal control of lysosomal enzyme release from human neutrophils. Effects of autonomic agents on enzyme release, phagocytosis, and cylic nucleotide levels. J Exp Med. 1974 Jun 1;139(6):1395–1414. doi: 10.1084/jem.139.6.1395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. JAFFE I. A. Comparison of the effect of plasmapheresis and penicillamine on the level of circulating rheumatoid factor. Ann Rheum Dis. 1963 Mar;22:71–76. doi: 10.1136/ard.22.2.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. JAFFE I. A. Intra-articular dissociation of the rheumatoid factor. J Lab Clin Med. 1962 Sep;60:409–421. [PubMed] [Google Scholar]
  14. Jaffe I. A., Merryman P., Ehrenfeld E. Further studies of the anti-viral effect of D-peniclllamine. Postgrad Med J. 1974 Aug;50 (Suppl 2):50–55. [PubMed] [Google Scholar]
  15. Kvarstein B. A methodological study of human leucocyte adhesiveness to glass beads. Scand J Clin Lab Invest. 1969 May;23(3):259–270. doi: 10.3109/00365516909077659. [DOI] [PubMed] [Google Scholar]
  16. Kvarstein B. The effect of temperature, mabolic inhibitors, andEDTA on pgocytosis of polystyrene latex particles by human leucocytes. Scand J Clin Lab Invest. 1969 Oct;24(3):271–277. doi: 10.3109/00365516909080162. [DOI] [PubMed] [Google Scholar]
  17. Liyanage S. P., Currey H. L. Failure of oral D-penicillamine to modify adjuvant arthritis or immune response in the rat. Ann Rheum Dis. 1972 Nov;31(6):521–521. doi: 10.1136/ard.31.6.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Maldykowa H., Chwalińska-Sadowska H., Luft S., Glińska-Urban D., Mikolajew M., Odrzywolska A., Jaworska H. Wyniki leczenia cuprenilem chorych na gościec przewlekły postepujacy. Reumatologia. 1972;10(1):9–21. [PubMed] [Google Scholar]
  19. Mowat A., Baum J. Chemotaxis of polymorphonuclear leukocytes from patients with diabetes mellitus. N Engl J Med. 1971 Mar 25;284(12):621–627. doi: 10.1056/NEJM197103252841201. [DOI] [PubMed] [Google Scholar]
  20. Roath S., Wills R. The effects of penicillamine on lymphocytes in culture. Postgrad Med J. 1974 Aug;50 (Suppl 2):56–59. [PubMed] [Google Scholar]
  21. Rosenfeld S. I., Baum J., Steigbigel R. T., Leddy J. P. Hereditary deficiency of the fifth component of complement in man. II. Biological properties of C5-deficient human serum. J Clin Invest. 1976 Jun;57(6):1635–1643. doi: 10.1172/JCI108434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. WROBLEWSKI F., LADUE J. S. Lactic dehydrogenase activity in blood. Proc Soc Exp Biol Med. 1955 Oct;90(1):210–213. doi: 10.3181/00379727-90-21985. [DOI] [PubMed] [Google Scholar]
  23. Wagner T., Abraham G., Baum J. The roles of IgG, IgM rheumatoid factor, and their complexes in the induction of polymorphonuclear leukocyte chemotactic factor from complement. J Clin Invest. 1974 Jun;53(6):1503–1511. doi: 10.1172/JCI107700. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES