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-2,4phenylmethyl-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.
- Cell proliferation
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Cancer Research