Lipopolysaccharide induces cell volume increase and migration of dendritic cells.
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 (K(Ca) 3.1) as putative regulators of immune cell volume regulation and migration was analyzed in LPS-challenged BMDCs. We found that the LPS-induced swelling of K(Ca) 3.1-deficient DCs was impaired when compared to WT DCs. Accordingly, the LPS-induced increase in [Ca(2+)](i) detected in WT DCs was reduced in K(Ca) 3.1-deficient DCs. Finally, directed migration of LPS-challenged K(Ca) 3.1-deficient DCs was low compared to WT DCs indicating that activation of K(Ca) 3.1 is involved in LPS-induced DC migration. These findings suggest that both TLR4 and K(Ca) 3.1 contribute to the migration of LPS-activated DCs as an important feature of the adaptive immune response.
Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
Sabine
S
Gröbner
Robert
R
Lukowski
Ingo B
IB
Autenrieth
Peter
P
Ruth
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D048429:Cell Size / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005260:Female; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496925:Kcnn4 protein, mouse; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D002118:Calcium
KCa3.1 (SK4, IK1, KCNN4) channel; Toll-like receptor 4 (TLR4); [Ca2+]i; intermediate conductance calcium-activated potassium channels