Histamine induces CD86 expression and chemokine production by human immature dendritic cells

Histamine induces CD86 expression and chemokine production by human immature dendritic cells
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DOI:
10.4049/jimmunol.166.10.6000
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发表时间:
2001-05-15
影响因子:
4.4
通讯作者:
Jeannin, P
Jeannin, P
中科院分区:
医学2区
文献类型:
--
作者:
Caron, G;Delneste, Y;Jeannin, P

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肥大细胞和未成熟树突状细胞(DC)在外周组织中密切接触。激活后,肥大细胞释放组胺,这是一种参与即时超敏反应的介质。因此,我们测试了组胺是否会影响人类DC的激活和成熟。组胺诱导CD86在未成熟DC上的表达呈剂量依赖性(在10(-7)M时显著)和瞬时性(在刺激24小时后达到最大值)。组胺也瞬间上调共刺激和辅助分子CD40、CD49d、CD54、CD80和MHC II类的表达。因此,暴露于组胺24小时的未成熟DC比未处理DC更有效地刺激记忆T细胞。此外,组胺诱导未成熟DC产生IL-6、IL-8、单核细胞化学引诱蛋白1和巨噬细胞炎症蛋白1 α,并上调IL-1 β、RANTES和巨噬细胞炎症蛋白1 β,但不上调tnf - α和IL-12 mRNA的表达。组胺通过H1和H2受体激活未成熟DC。然而,组胺处理的DC不具有完全成熟细胞的表型,因为它们在趋化因子受体CCR5、CCR7和CXC趋化因子受体4的表达和CD83的表达方面都没有显着变化。这些数据表明,组胺激活未成熟DC并诱导趋化因子的产生,从而提示组胺通过刺激常驻DC,可能局部参与T细胞刺激和与过敏性疾病相关的晚期炎症反应。
Mast cells and immature dendritic cells (DC) are in close contact in peripheral tissues. Upon activation, mast cells release histamine, a mediator involved in the immediate hypersensitivity reaction. We therefore tested whether histamine could affect human DC activation and maturation. Histamine induces CD86 expression on immature DC in a dose-dependent (significant at 10(-7) M) and transient manner (maximal after 24-h stimulation). Histamine also transiently up-regulates the expression of the costimulatory and accessory molecules, CD40, CD49d, CD54, CD80, and MHC class II. As a consequence, immature DC exposed for 24 h to histamine stimulate memory T cells more efficiently than untreated DC. In addition, histamine induces a potent production of IL-6, IL-8, monocyte chemoattractant protein 1, and macrophage-inflammatory protein 1 alpha by immature DC and also up-regulates IL-1 beta, RANTES, and macrophage-inflammatory protein 1 beta but not TNF-alpha and IL-12 mRNA expression. Histamine activates immature DC through both the H1 and H2 receptors. However, histamine-treated DC do not have a phenotype of fully mature cells, as they do neither show significant changes in the expression of the chemokine receptors, CCR5, CCR7 and CXC chemokine receptor 4, nor expression of CD83 de novo. These data demonstrate that histamine activates immature DC and induces chemokine production, thereby suggesting that histamine, via stimulation of resident DC, may participate locally in T cell stimulation and in the late inflammatory reaction associated with allergic disorders.