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

Abstract

Histidine decarboxylase (HDC), the only enzyme capable of synthetizing 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 the 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--aFMH) 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.

Histamine

“…For many years there have been persistent observations of histamine in other, nonbasophilic, circulating cells; lymphocytes, monocytes, and platelets appear to contain very low levels of histamine (Table I). [7][8][9][10] The significance of this observation will be covered in more detail later.…”

“…The importance of histamine in regulating the function of lymphocytes, monocytes, or platelets has been inferred from previous studies. 10,25,26 Because HDC is necessary for the synthesis of histamine, the use of α-fluoro-methyl histidine provides a relatively specific means with which to inhibit its production. The compound N´Ndiethyl-2-4-(phenylmethyl) phenoxyethan-amine-HCl has been characterized as an inhibitor of the H IC "receptor" and as a cell permanent antagonist that can be used in conjunction with α-fluoro-methyl histidine to define the functional role of intracellular histamine.…”

Secondary Cutaneous Infiltration in B Cell Chronic Lymphocytic Leukemia

“…Bencsáth et al [15]found that the preformed pool of histamine interferes with cellular proliferation. HDC is an obligatory enzyme in histamine synthesis.…”

Histamine H4 receptors in the gastrointestinal tract

“…Histamine is synthetized from L-histidine by L-histidine decarboxylase and is stored in the granules of mast cells (MCs) and basophils, the main sources of histamine (Endo, 1982;Jones and Kearns, 2011). Enterochromaffin-like cells, histaminergic neurons, lymphocytes, monocytes, platelets and neutrophils also express L-histidine decarboxylase and are capable of producing, but not storing, high amounts of histamine (Snyder and Epps, 1968;Vanhala et al, 1994;Bencsath et al, 1998;Jutel et al, 2009;Alcaniz et al, 2013). Histamine exerts its actions by binding to four GPCRs that are differentially expressed throughout the body and designated as the H1, H2, H3 and H4 receptors.…”