Plasticity of Histamine H_1 Receptor Expression in Human AAononuclear Phagocytes

摘要

Background: Histamine plays a pivotal role in allergic inflammation by inducing proinflam-matory and immunoregulatory effects which are primarily mediated by activation of the H_1 receptor. The responses elicited by histamine in human inflammatory cells are quite different, suggesting that the expression of H_1 receptors can be differently regulated. Methods and Results: To examine the expression of the H_1 receptor in human mononuclear phagocytes, we explored accumulation of mRNA for the Hj receptor in a model of macrophages developed in vitro by incubation of blood monocytes for 10 days in the presence of 20% FCS. Quantitative RT-PCR experiments showed that the mRNA for the H_1 receptor increased 15-fold in differentiated macrophages as compared to blood monocytes. Incubation of differentiating macrophages with budesonide (0.1-1 muM) for 24 h resulted in approximately 50 percent inhibition of H_1 receptor expression. The receptor upregulated was functionally active since incubation of macrophages with histamine (1 muM) induced a significant increase in intracellular Ca~(2+) that was blocked by the H_1 antagonist levocetirizine. Histamine induced a concentration-dependent production of IL-8 in macrophages, whereas this response was not detectable in the precursor monocytes. Conclusions: These data indicate that differentiation of monocytes into macrophages, either in vivo in the lung or in vitro, is associated with upregulation of the histamine H_1 receptor.