PMID- 23145172
OWN - NLM
STAT- MEDLINE
DCOM- 20130625
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 11
DP  - 2012
TI  - Sphingosine 1-phosphate modulates antigen capture by murine Langerhans cells via 
      the S1P2 receptor subtype.
PG  - e49427
LID - 10.1371/journal.pone.0049427 [doi]
LID - e49427
AB  - Dendritic cells (DCs) play a pivotal role in the development of cutaneous contact 
      hypersensitivity (CHS) and atopic dermatitis as they capture and process antigen 
      and present it to T lymphocytes in the lymphoid organs. Recently, it has been 
      indicated that a topical application of the sphingolipid sphingosine 1-phosphate 
      (S1P) prevents the inflammatory response in CHS, but the molecular mechanism is 
      not fully elucidated. Here we indicate that treatment of mice with S1P is 
      connected with an impaired antigen uptake by Langerhans cells (LCs), the initial 
      step of CHS. Most of the known actions of S1P are mediated by a family of five 
      specific G protein-coupled receptors. Our results indicate that S1P inhibits 
      macropinocytosis of the murine LC line XS52 via S1P(2) receptor stimulation 
      followed by a reduced phosphatidylinositol 3-kinase (PI3K) activity. As 
      down-regulation of S1P(2) not only diminished S1P-mediated action but also 
      enhanced the basal activity of LCs on antigen capture, an autocrine action of S1P 
      has been assumed. Actually, S1P is continuously produced by LCs and secreted via 
      the ATP binding cassette transporter ABCC1 to the extracellular environment. 
      Consequently, inhibition of ABCC1, which decreased extracellular S1P levels, 
      markedly increased the antigen uptake by LCs. Moreover, stimulation of 
      sphingosine kinase activity, the crucial enzyme for S1P formation, is connected 
      not only with enhanced S1P levels but also with diminished antigen capture. These 
      results indicate that S1P is essential in LC homeostasis and influences skin 
      immunity. This is of importance as previous reports suggested an alteration of 
      S1P levels in atopic skin lesions.
FAU - Japtok, Lukasz
AU  - Japtok L
AD  - Faculty of Mathematics and Natural Science, Department of Toxicology, Institute 
      of Nutritional Science, University of Potsdam, Potsdam, Germany.
FAU - Schaper, Katrin
AU  - Schaper K
FAU - Baumer, Wolfgang
AU  - Baumer W
FAU - Radeke, Heinfried H
AU  - Radeke HH
FAU - Jeong, Se Kyoo
AU  - Jeong SK
FAU - Kleuser, Burkhard
AU  - Kleuser B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121108
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antigens)
RN  - 0 (Lysophospholipids)
RN  - 0 (Receptors, Lysosphingolipid)
RN  - 26993-30-6 (sphingosine 1-phosphate)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - NGZ37HRE42 (Sphingosine)
SB  - IM
MH  - Administration, Topical
MH  - Animals
MH  - Antigens/immunology
MH  - Cells, Cultured
MH  - Dermatitis, Contact/*drug therapy
MH  - Endocytosis/drug effects
MH  - Female
MH  - Homeostasis
MH  - Langerhans Cells/*immunology
MH  - Lysophospholipids/administration & dosage/pharmacology/*therapeutic use
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Receptors, Lysosphingolipid/physiology
MH  - Skin/*immunology
MH  - Sphingosine/administration & dosage/*analogs & 
      derivatives/pharmacology/therapeutic use
PMC - PMC3493526
COIS- Competing Interests: SKJ is employed by Neopharm Co. Ltd. Neopharm provided the 
      Sphk-activator K6PC-5 for this study. There are no further patents, products in 
      development or marketed products to declare. This does not alter the authors' 
      adherence to all the PLOS ONE policies on sharing data and materials, as detailed 
      online in the guide for authors.
EDAT- 2012/11/13 06:00
MHDA- 2013/06/26 06:00
PMCR- 2012/11/08
CRDT- 2012/11/13 06:00
PHST- 2012/08/08 00:00 [received]
PHST- 2012/10/08 00:00 [accepted]
PHST- 2012/11/13 06:00 [entrez]
PHST- 2012/11/13 06:00 [pubmed]
PHST- 2013/06/26 06:00 [medline]
PHST- 2012/11/08 00:00 [pmc-release]
AID - PONE-D-12-23704 [pii]
AID - 10.1371/journal.pone.0049427 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(11):e49427. doi: 10.1371/journal.pone.0049427. Epub 2012 Nov 8.