Advertisement

Histidine decarboxylase in peripheral lymphocytes of healthy individuals and chronic lymphoid leukemia patients

Possible involvement of intracellular histamine in the regulation of lymphocyte proliferation
  • Márta Bencsáth
  • Katalin PáLóczi
  • Csaba Szalai
  • Andrea Szenthe
  • Júlia Szeberényi
  • András Falus
Article

Abstract

Histidine decarboxylase (HDC), the only enzyme capable of synthesis of histamine, has been found in many proliferating cells and tissues suggesting a role of histamine in cellular proliferation. In this study expression of HDC and the significance of histamine in the proliferation of peripheral lymphocytes of five healthy persons and six patients with chronic lymphoid leukemia (CLL) was examined. Expression of HDC mRNA and HDC protein was proved by reverse transcriptase polymerase chain reaction and by immunoblot, respectively. The role of histamine was studied in proliferation assays in the presence of irreversible inhibitor of the HDC (alpha-fluoromethylhistidine-FMH) and also by competing for the intracellular binding sites of histamine using N,N-diethyl-2,4-phenylmethyl-phenoxy-ethanamine-HCl (DPPE). By inhibiting the HDC enzyme activity by FMH and blocking the intracellular action of histamine by DPPE, a significant decrease in cell proliferation was observed in mitogen stimulated lymphocytes of healthy donors. In CLL patients the proliferation of leukemic lymphocytes was significantly inhibited by blocking the binding of histamine to intracellular binding sites by DPPE, but not by FMH inhibiting only the de novo histamine formation. The observations suggest that HDC has functional relevance in lymphocytes, since mitogen induced lymphocyte proliferation of healthy donors is mainly enhanced by de novo synthesis and subsequent action of intracellular histamine. Alternatively, in constitutively proliferating chronic lymphoid leukemia cells we suggest that the preformed pool but not the de novo synthesized intracellular histamine interferes with cellular proliferation.

Key words

histamine lymphocyte cell proliferation leukemia 

References

  1. 1.
    Brandes LJ, LaBella FS: Histamine and calcium are independently regulated intracellular mediators of lymphocyte mitoge-nesis. Biochem Biophys Res Commun 182:786–793, 1992.PubMedCrossRefGoogle Scholar
  2. 2.
    Garcia Caballero M, Neugebauer E, Rodriguez F, et al: Histamine synthesis and content in benign and malignant breast tumors. Surg Oncol 3:167–173, 1994.CrossRefGoogle Scholar
  3. 3.
    Brandes LJ, Beecroft WA, Hogg GR: Stimulation of in vivo tumor growth and phorbol ester induced inflammation by N,Ndiethyl-2[4-phenylmethyl)phenoxy]ethanamine HC1, a potent ligand for intracellular histamine receptors. Biochem Biophys Res Commun 179:1297–1304, 1991.PubMedCrossRefGoogle Scholar
  4. 4.
    Glavin GB, Brandes LJ: Antiulcerogenic and antisecretory effects of a novel diphenylmethane derivative and antiestrogen binding site ligand. Can J Physiol Pharmacol 66:1139–1143, 1988.PubMedGoogle Scholar
  5. 5.
    Watanabe T, Yamatodani A, Kazutaka M, Wada H: Pharmacology of-fluoromethylhistidine, a specific inhibitor of histidine decarboxylase. TIBS 11:363–367, 1990.Google Scholar
  6. 6.
    Kondo S, Imamura I, Shinomura Y, et al: Determination of histidine decarboxylase mRNA in various rat tissues by the poly-merase chain reaction. Inflamm Res 44:111–115, 1995.PubMedCrossRefGoogle Scholar
  7. 7.
    Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159, 1987.PubMedCrossRefGoogle Scholar
  8. 8.
    Denizot F, Lang R: Rapid colorimetric assay for cell growth and survival - Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods 89:271–277, 1986.PubMedCrossRefGoogle Scholar
  9. 9.
    Kollonitsch J, Patchett AA, Marburg S: Selective inhibitors of biosynthesis of aminergic neurotransmitters. Nature 274:906–908, 1978.PubMedCrossRefGoogle Scholar
  10. 10.
    Brandes LJ, Bogdanovic RP, Cawker MD, LaBella FS: Histamine and growth: interaction of antiestrogen binding site lig-ands with a novel histamine site that may be associated with calcium channels. Cancer Res 47:4025–4031, 1987.PubMedGoogle Scholar
  11. 11.
    Glavin GB, Gerrard JM: Characterization of the gastroprotec-tive effects of N,N-diethyl-2-[4-(phenylmethyl)phenoxy]-etha-namine hydrochloride, a non-Hl/non-H2 histamine antagonist. Digestion 47:143–148, 1990.PubMedCrossRefGoogle Scholar
  12. 12.
    Brandes LJ, Arron RJ, Bogdanovic RP: Stimulation of malignant growth in rodents by antidepressant drugs at clinically relevant doses. Cancer Res 52:3796–3800, 1992.PubMedGoogle Scholar
  13. 13.
    Bartholeyns J, Bouclier M: Involvement of histamine in growth of mouse and rat tumors: antitumoral properties of monofluo-romethylhistidine, an enzyme-activated irreversible inhibitor of histidine decarboxylase. Cancer Res 44:639–645, 1984.PubMedGoogle Scholar
  14. 14.
    Brandes LJ, LaBella FS, Warrington RC: Increased therapeutic index of antineoplastic drugs in combination with intracellular histamine antagonists. J Natl Cancer Inst 83:1329–1336, 1991.PubMedCrossRefGoogle Scholar
  15. 15.
    Brandes LJ, Bracken SP, Ramsey EW: N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine in combination with cyclo-phosphamide: an active, low-toxicity regimen for metastatic hormonally unresponsive prostate cancer. J Clin Oncol 13:1398–1403, 1995.PubMedGoogle Scholar
  16. 16.
    Brandes LI, Gerrard JM, Bogdanovic RP, et al: Correlation of the antiproliferative action of diphenylmethane-derivative antiestrogen binding site ligands with antagonism of histamine binding but not of protein kinase C-mediated phosphorylation. Cancer Res 48:3954–3958, 1988.PubMedGoogle Scholar
  17. 17.
    Saxena SP, McNicol A, Brandes LJ, et al: A role for intracellular histamine in collagen-induced platelet aggregation. Blood 75:407–414, 1990.PubMedGoogle Scholar

Copyright information

© Arányi Lajos Foundation 1998

Authors and Affiliations

  • Márta Bencsáth
    • 1
  • Katalin PáLóczi
    • 2
  • Csaba Szalai
    • 3
  • Andrea Szenthe
    • 1
  • Júlia Szeberényi
    • 1
  • András Falus
    • 1
  1. 1.Department of Genetics, Cell- and ImmunobiologySemmelweis University of MedicineBudapestHungary
  2. 2.National Institute of Hematology and ImmunologyBudapest
  3. 3.Pal HeimChildren’s HospitalBudapestHungary

Personalised recommendations