PMID- 12475762
OWN - NLM
STAT- MEDLINE
DCOM- 20030121
LR  - 20200930
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 284
IP  - 1
DP  - 2003 Jan
TI  - Inhibition of interferon-gamma expression by osmotic shrinkage of peripheral 
      blood lymphocytes.
PG  - C200-8
AB  - A hypertonic environment, as it prevails in renal medulla or in hyperosmolar 
      states such as hyperglycemia of diabetes mellitus, has been shown to impair the 
      immune response, thus facilitating the development of infection. The present 
      experiments were performed to test whether hypertonicity influences activation of 
      T lymphocytes. To this end, peripheral blood lymphocytes (PBL) of cytomegalovirus 
      (CMV)-positive donors were stimulated by human leukocyte antigen 
      (HLA)-A2-restricted CMV epitope NLVPMVATV to produce interferon (IFN)-gamma at 
      varying extracellular osmolarity. As a result, increasing extracellular 
      osmolarity during exposure to the CMV antigen indeed decreased IFN-gamma 
      formation. Addition of NaCl was more effective than urea. A 50% inhibition was 
      observed at 350 mosM by addition of NaCl. The combined application of the Ca(2+) 
      ionophore ionomycin (1 microg/ml) and the phorbol ester phorbol 12-myristate 
      13-acetate (PMA; 5 microg/ml) stimulated IFN-gamma production, an effect again 
      reversed by hyperosmolarity. Moreover, hyperosmolarity abrogated the stimulating 
      effect of ionomycin (1 microg/ml) and PMA (5 microg/ml) on the transcription 
      factors activator protein (AP)-1, nuclear factor of activated T cells (NFAT), and 
      NF-kappaB but not Sp1. In conclusion, osmotic cell shrinkage blunts the 
      stimulatory action of antigen exposure on IFN-gamma production, an effect 
      explained at least partially by suppression of transcription factor activation.
FAU - Lang, K S
AU  - Lang KS
AD  - Department of Immunology, University of Tubingen, Gmelinstrasse 5, D-72076 
      Tubingen, Germany.
FAU - Weigert, C
AU  - Weigert C
FAU - Braedel, S
AU  - Braedel S
FAU - Fillon, S
AU  - Fillon S
FAU - Palmada, M
AU  - Palmada M
FAU - Schleicher, E
AU  - Schleicher E
FAU - Rammensee, H-G
AU  - Rammensee HG
FAU - Lang, F
AU  - Lang F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Apoptosis/physiology
MH  - Cell Size/physiology
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Gene Expression Regulation/*physiology
MH  - Humans
MH  - Interferon-gamma/*antagonists & inhibitors/*biosynthesis
MH  - Osmolar Concentration
MH  - Osmosis/physiology
MH  - T-Lymphocytes/*cytology/physiology
EDAT- 2002/12/12 04:00
MHDA- 2003/01/22 04:00
CRDT- 2002/12/12 04:00
PHST- 2002/12/12 04:00 [pubmed]
PHST- 2003/01/22 04:00 [medline]
PHST- 2002/12/12 04:00 [entrez]
AID - 284/1/C200 [pii]
AID - 10.1152/ajpcell.00259.2002 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2003 Jan;284(1):C200-8. doi: 
      10.1152/ajpcell.00259.2002.