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Keywords:

  • [Ca2+]i;
  • intermediate conductance calcium-activated potassium channels;
  • KCa3.1 (SK4, IK1, KCNN4) channel;
  • Toll-like receptor 4 (TLR4)

ABSTRACT

Migration of dendritic cells (DCs) plays an important role in T-cell-mediated adaptive immune responses. Lipopolysaccharide (LPS) sensed by Toll-like receptor 4 (TLR4) serves as a signal for DC migration. We analyzed LPS-induced DC volume changes preceding the directed movement towards chemoattractants. Treatment with LPS resulted in rapid, prolonged cell swelling in wild-type (WT), but not in TLR4−/− bone marrow-derived (BM) DCs indicating that TLR4 signaling is essential for LPS-induced swelling. As a consequence, LPS-treatment enhanced the migratory activity along a chemokine (CCL21)-gradient in WT, but not in TLR4-deficient BMDCs suggesting that the LPS/TLR4-induced swelling response facilitates DC migration. Moreover, the role of calcium-activated potassium channels (KCa3.1) as putative regulators of immune cell volume regulation and migration was analyzed in LPS-challenged BMDCs. We found that the LPS-induced swelling of KCa3.1-deficient DCs was impaired when compared to WT DCs. Accordingly, the LPS-induced increase in [Ca2+]i detected in WT DCs was reduced in KCa3.1-deficient DCs. Finally, directed migration of LPS-challenged KCa3.1-deficient DCs was low compared to WT DCs indicating that activation of KCa3.1 is involved in LPS-induced DC migration. These findings suggest that both TLR4 and KCa3.1 contribute to the migration of LPS-activated DCs as an important feature of the adaptive immune response.