Expression of kinin B₁ and B₂ receptors in immature, monocyte-derived dendritic cells and bradykinin-mediated increase in intracellular Ca²⁺ and cell migration

The kinins, bradykinin (BK) and Lysdes[ Arg⁹]-BK, are important inflammatory mediators that act via two specific G protein-coupled kinins, B₁ and B₂ receptors (B₂R). Kinins influence the activity of immune cells by stimulating the synthesis of cytokines, eicosanoids, and chemotactic factors. Whether human dendritic cells (DC) express kinin receptors and whether kinins influence DC function are unknown. Fluorescence immunocytochemistry and RT-PCR were used to demonstrate that immature human monocyte-derived DC (hMo-DC) constitutively expressed kinins B₁R and B₂R. Kinin receptor expression was induced on the 3rd and 4th days of culture during differentiation of hMo-DC from monocytes and was not dependent on the presence of IL-4 or GM-CSF. Although monocytes also expressed B₂R mRNA, the protein was not detected. The kinin agonists BK and Lys-des[Arg⁹]-BK up-regulated the expression of their respective receptors. BK, acting via the B₂R, increased intracellular Ca²⁺, as visualized by confocal microscopy using the fluorescent Ca²⁺ dye, Fluor-4 AM. Evaluation of migration in Trans-well chambers demonstrated significant enhancement by BK of migration of immature hMo-DC, which was B₂R-dependent. However, kinins did not induce maturation of hMo-DC. The novel finding that kinin receptors are constitutively expressed in immature hMo-DC suggests that these receptors may be expressed in the absence of proinflammatory stimuli. BK, which increases the migration of immature hMo-DC in vitro, may play an important role in the migration of immature DC in noninflammatory conditions and may also be involved in the recruitment of immature DC to sites of inflammation.