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 Lys-des[Arg(9)]-BK, are important inflammatory mediators that act via two specific G protein-coupled kinins, B(1) and B(2) receptors (B(2)R). 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 B(1)R and B(2)R. 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 B(2)R mRNA, the protein was not detected. The kinin agonists BK and Lys-des[Arg(9)]-BK up-regulated the expression of their respective receptors. BK, acting via the B(2)R, increased intracellular Ca(2+), as visualized by confocal microscopy using the fluorescent Ca(2+) dye, Fluor-4 AM. Evaluation of migration in Trans-well chambers demonstrated significant enhancement by BK of migration of immature hMo-DC, which was B(2)R-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.
Bertram
Cornelia M
CM
Lung Institute of Western Australia and Centre for Asthma, Allergy and Respiratory Research, The University of Western Australia, Perth, Australia.
Baltic
Svetlana
S
Misso
Neil L
NL
Bhoola
Kanti D
KD
Foster
Paul S
PS
Thompson
Philip J
PJ
Fogel-Petrovic
Mirjana
M
D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D007424:Intracellular Fluid / Q000378:metabolism; D007609:Kallidin / Q000031:analogs & derivatives / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D043783:Receptor, Bradykinin B1 / Q000819:agonists / Q000096:biosynthesis*; D043782:Receptor, Bradykinin B2 / Q000819:agonists / Q000096:biosynthesis*
C508598:IL4 protein, human; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D015847:Interleukin-4; D007609:Kallidin; C052787:kallidin, des-Arg(10)-; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D001920:Bradykinin; D002118:Calcium