PMID- 16366734
OWN - NLM
STAT- MEDLINE
DCOM- 20060413
LR  - 20181201
IS  - 1545-7885 (Electronic)
IS  - 1544-9173 (Print)
IS  - 1544-9173 (Linking)
VI  - 4
IP  - 1
DP  - 2006 Jan
TI  - Activation of NK cells by an endocytosed receptor for soluble HLA-G.
PG  - e9
LID - e9
AB  - Signaling from endosomes is emerging as a mechanism by which selected receptors 
      provide sustained signals distinct from those generated at the plasma membrane. 
      The activity of natural killer (NK) cells, which are important effectors of 
      innate immunity and regulators of adaptive immunity, is controlled primarily by 
      receptors that are at the cell surface. Here we show that cytokine secretion by 
      resting human NK cells is induced by soluble, but not solid-phase, antibodies to 
      the killer cell immunoglobulin-like receptor (KIR) 2DL4, a receptor for human 
      leukocyte antigen (HLA)-G. KIR2DL4 was constitutively internalized into 
      Rab5-positive compartments via a dynamin-dependent process. Soluble HLA-G was 
      endocytosed into KIR2DL4-containing compartments in NK cells and in 293T cells 
      transfected with KIR2DL4. Chemokine secretion induced by KIR2DL4 transfection 
      into 293T cells occurred only with recombinant forms of KIR2DL4 that trafficked 
      to endosomes. The profile of genes up-regulated by KIR2DL4 engagement on resting 
      NK cells revealed a proinflammatory/proangiogenic response. Soluble HLA-G induced 
      secretion of a similar set of cytokines and chemokines. This unique stimulation 
      of resting NK cells by soluble HLA-G, which is endocytosed by KIR2DL4, implies 
      that NK cells may provide useful functions at sites of HLA-G expression, such as 
      promotion of vascularization in maternal decidua during early pregnancy.
FAU - Rajagopalan, Sumati
AU  - Rajagopalan S
AD  - Laboratory of Immunogenetics, National Institute of Allergy and Infectious 
      Diseases, National Institutes of Health, Rockville, Maryland, USA.
FAU - Bryceson, Yenan T
AU  - Bryceson YT
FAU - Kuppusamy, Shanmuga P
AU  - Kuppusamy SP
FAU - Geraghty, Daniel E
AU  - Geraghty DE
FAU - van der Meer, Arnold
AU  - van der Meer A
FAU - Joosten, Irma
AU  - Joosten I
FAU - Long, Eric O
AU  - Long EO
LA  - eng
SI  - GENBANK/DQ266438
SI  - GENBANK/M90683
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - PLoS Biol
JT  - PLoS biology
JID - 101183755
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-8)
RN  - 0 (KIR2DL4 protein, human)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Receptors, KIR)
RN  - 0 (Receptors, KIR2DL4)
RN  - 0 (Receptors, KIR2DL5)
RN  - EC 3.6.5.2 (rab5 GTP-Binding Proteins)
RN  - EC 3.6.5.5 (Dynamins)
SB  - IM
CIN - PLoS Biol. 4:e30.
MH  - Chemokines/biosynthesis
MH  - Cytokines/biosynthesis
MH  - Dynamins/pharmacology
MH  - Endocytosis/*physiology
MH  - Humans
MH  - Interleukin-8/metabolism
MH  - Killer Cells, Natural/drug effects/*physiology
MH  - Molecular Sequence Data
MH  - Receptors, Immunologic/*physiology
MH  - Receptors, KIR
MH  - Receptors, KIR2DL4
MH  - Receptors, KIR2DL5
MH  - Solubility
MH  - Up-Regulation
MH  - rab5 GTP-Binding Proteins/physiology
PMC - PMC1318474
EDAT- 2005/12/22 09:00
MHDA- 2006/04/14 09:00
PMCR- 2005/12/27
CRDT- 2005/12/22 09:00
PHST- 2005/03/29 00:00 [received]
PHST- 2005/10/26 00:00 [accepted]
PHST- 2005/12/22 09:00 [pubmed]
PHST- 2006/04/14 09:00 [medline]
PHST- 2005/12/22 09:00 [entrez]
PHST- 2005/12/27 00:00 [pmc-release]
AID - 05-PLBI-RA-0250R2 [pii]
AID - 10.1371/journal.pbio.0040009 [doi]
PST - ppublish
SO  - PLoS Biol. 2006 Jan;4(1):e9. doi: 10.1371/journal.pbio.0040009.