Back
Acta Physiologica 2013; Volume 207, Supplement 694
92nd Annual Meeting of the German Physiological Society
3/2/2013-3/5/2013
Heidelberg, Germany
ALTERED REGULATION OF CYTOSOLIC CA2+ CONCENTRATION IN DENDRITIC CELLS FROM KLOTHO HYPOMORPHIC MICE
Abstract number: P041
Nurbaeva
1
*M.
, Shumilina
1
E., Yang
1
W., Schmid
1
E., Leibrock
1
C., Lang
1
F.
1
University of Tuebingen, Department of Physiology, Tuebingen, Germany
Background:
Function of dendritic cells (DCs), antigen-presenting cells regulating naïve T-cells, is regulated by cytosolic Ca2+ concentration ([Ca2+]i). [Ca2+]i is increased by store operated Ca2+ entry and decreased by K+-independent (NCX) and K+-dependent (NCKX) Na+/Ca2+ exchangers. NCKX exchangers are stimulated by immunosuppressive 1,25(OH)2D3. Formation of 1,25(OH)2D3 is inhibited by anti-aging protein klotho. Thus, 1,25(OH)2D3 plasma levels are excessive in klotho-deficient mice (
klothohm
). The present study explored whether klotho-deficiency modifies [Ca2+]i regulation in DCs.
Methods/Results:
DCs were isolated from bone marrow of
klothohm
mice and corresponding wild type mice (
klotho+/+
) and cultured for 7-9 days with GM-CSF. According to MHCII and CD86 expression, differentiation and lipopolysaccharide (LPS)-induced maturation was similar in
klothohm
and
klotho+/+
DCs. However, NCKX activity was significantly enhanced in
klothohm
DCs. The [Ca2+]i increase upon acute application of LPS (1 µg/ml) was significantly lower in
klothohm
DCs than in
klotho+/+
DCs, a difference reversed by NCKX-blocker 3’,4’-dichlorobenzamyl (DBZ, 10 µM). CCL21-dependent migration was significantly less in
klothohm
DCs than in
klotho+/+
DCs. NCKX activity could be enhanced by pretreatment of
klotho+/+
DC precursors with 1,25(OH)2D3 the first 2 days after isolation from bone marrow. Feeding
klothohm
mice a vitamin D deficient diet decreased NKCX activity, augmented LPS-induced increase of [Ca2+]i, and enhanced migration of
klothohm
DCs, thus dissipating the differences between
klothohm
DCs and
klotho+/+
DCs.
Conclusions:
Klotho deficiency up-regulates Na+/Ca2+ exchange activity and thus blunts the increase of [Ca2+]i following LPS exposure and CCL21-mediated migration. The effects are in large part due to excessive 1,25(OH)2D3 formation.
To cite this abstract, please use the following information:
Acta Physiologica 2013; Volume 207, Supplement 694 :P041