A Study on Immunoregulatory Action of Endogenously Formed Histamine

众所周知，组胺发挥多种免疫调节作用。然而，所有这些结果都是基于实验，其中组胺被外源性地加入免疫系统。据信，在用变应原-反应素复合物激活细胞时，胺从肥大细胞和嗜碱性粒细胞释放。我们在本研究中发现，组胺通过组氨酸脱羧酶从头合成，组氨酸脱羧酶在有丝分裂原或过敏原刺激的巨噬细胞和T淋巴细胞中被诱导（#1）。这里还表明，由巨噬细胞和T淋巴细胞产生的组胺调节免疫反应。也就是说，有丝分裂原依赖的淋巴细胞胚细胞生成是由系统本身产生的组胺调节的（#2）。在反应的早期阶段，当胺的产量低时，它通过与位于某些免疫细胞的细胞表面上的H_1受体相互作用来刺激反应。随后，当大量胺在系统中积累时，它又通过激活其在未知细胞上的H_2受体来抑制反应。然后，我们研究了组胺介导的免疫反应刺激的性质。结果表明，巨噬细胞产生的白细胞介素1受组胺的调节，组胺通过与H_1受体的相互作用由巨噬细胞产生（#3）。研究还表明，组胺刺激巨噬细胞合成IL-1是通过细胞外Ca^2+的掺入和细胞内cAMP生成的增加来介导的（# 4），这些结果表明组胺是一种新发现的内源性免疫调节剂。

It is well known that histamine exerts a variety of immunoregulatory actions. However all of these results are based on the experiments, in which histamine is added exogenously into the immune systems. The amine is believed to be released from mast cells and basophils upon activation of the cells with allergen-reagin complex. we found in the present study that histamine is synthesized de novo through histidine decarboxylase, which is induced in mitogen- or allergen-stimulated macrophages and T lymphocytes (# 1). It was also shown here that histamine, thus produced by macrophages and T lymphocytes, modulates immune reactions. That is, mitogen-dependent lymphocyte blastogenesis is modulated by histamine produced in the system per se (# 2). In the early stage of the reaction, when the production of the amine is low, it stimulates the reaction via interaction with its H_1-receptors located on the cell-surface of certain immune cells. Later, when a large amount of amine is accumulated in the system, it suppresses, in turn, the reaction through activation of its H_2-receptors on unidentified cells. We then investigated the nature of the histamine-mediated stimulation of the immune responses. The results obtained showed that interleukin 1 production by macrophages is modulated by histamine produced by the cells per se via interaction with its H_1-receptors (# 3). It was also shown that the histamine-stimulated IL-1 synthesis by macrophages is mediated by incorporation of extracellular Ca^<2+> and by increase in production of cyclic AMP in the cell (# 4).These results suggest that histamine is a newly-found edogenous immunoregulator.