Anti-CD3 antibody induces histidine-decarboxylase gene expression in human lymphocytes

摘要

Histamine, synthetized by histidine decarboxylase (HDC) has been found in many proliferating cells, including haematopoetic cells and activated murine spleen lymphocytes suggesting a role of this monoamine in T-lymphocyte maturation and proliferation, as well. In this study HDC gene expression and enzyme protein were examined in anti-CD3 treated (activated) human Th1 leukemic cell line (Jurkat) and in peripheral lymphocytes of human healthy adult individuals. HDC, g-IFN, actin mRNAs and HDC enzyme protein levels were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and by western blotting, respectively. The expression of HDC during the T cell activation was studied using anti-CD3 antibody for different incubation times. We have shown that both Jurkat and healthy adult peripheral lymphocytes have a low constitutive HDC gene expression which can be further stimulated by monoclonal antibody against CD3, a part of T lymphocyte receptor. There was a concomitant increase in the γ-IFN and a slight decrease in the actin expression. The detection of HDC protein by western blotting showed marked difference between the T cell line (Jurkat) and the healthy lymphocytes; the HDC protein was found in much higher amount in the leukemic cell line than in the healthy T cells proving the role of intracellular histamine in the malignant cell proliferation. Histamine generating enzyme (HDC) is stored not only in mast cells, but in many different tissues undergoing rapid proliferation and growth suggesting that histamine a ubiquitously occuring local hormone, can function as a growth factor and chemical mediator, too. HDC expression in activated T cells suggests that intracellular histamine has a prominent role of T-lymphocyte activation and, as a newly recognised intracrine/autocrine signal transduction system has close relation to the regulation of cell division.