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

Mast cells and immature dendritic cells (DC) are in close contact in periph eral tissues. Upon activation, mast cells release histamine, a mediator inv olved in the immediate hypersensitivity reaction. We therefore tested wheth er histamine could affect human DC activation and maturation. Histamine ind uces CD86 expression on immature DC in a dose-dependent (significant at 10( -7) M) and transient manner (maximal after 24-h stimulation). Histamine als o transiently up-regulates the expression of the costimulatory and accessor y molecules, CD40, CD49d, CD54, CD80, and MHC class II. As a consequence, i mmature DC exposed for 24 h to histamine stimulate memory T cells more effi ciently than untreated DC. In addition, histamine induces a potent producti on of IL-6, IL-8, monocyte chemoattractant protein 1, and macrophage-inflam matory protein 1 alpha by immature DC and also up-regulates IL-1 beta, RANT ES, 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 e xpression of CD83 de novo. These data demonstrate that histamine activates immature DC and induces chemokine production, thereby suggesting that hista mine, via stimulation of resident DC, may participate locally in T cell sti mulation and in the late inflammatory reaction associated with allergic dis orders.