PMID- 16037391
OWN - NLM
STAT- MEDLINE
DCOM- 20051215
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 106
IP  - 10
DP  - 2005 Nov 15
TI  - Functional aberrant expression of CCR2 receptor on chronically activated NK cells 
      in patients with TAP-2 deficiency.
PG  - 3465-73
AB  - Chemokines play a pivotal role in homeostatic and inflammatory migration of naive 
      and activated natural killer (NK) subsets. Recent studies have shown that 
      aberrant chemokine receptor expression on certain immune cells underlies the 
      pathogenesis of clinical conditions in which recruitment of such cells is 
      altered. Progressive accumulation of activated NK cells, subsequently resulting 
      in the formation of chronic granulomatous lesions in the respiratory tract and 
      the skin, has been described in a number of patients with transporter associated 
      with antigen processing 2 (TAP-2) deficiency in the later stages of disease. 
      Therefore, the goal of the present study was to elucidate whether the 
      dysregulation of chemoattracting receptor expression on NK cells could explain 
      abnormal navigation of these cells in TAP-2 deficiency. High-throughput proteomic 
      comparison, followed by verification with flow cytometry, revealed that 
      chronically activated NK cells derived from 3 newly identified patients with 
      TAP-2 deficiency consistently expressed aberrant levels of CC chemokine receptor 
      2 (CCR2) chemokine receptor in vitro and in vivo. This expression pattern 
      translated into specific responsiveness of chronically activated NK cells derived 
      from patients with TAP-2 deficiency to multiple ligands of CCR2. Moreover, the in 
      vivo elevated levels of interleukin-2 (IL-2) and monocyte chemoattractant 
      protein-1 (MCP-1) detected in serum and bronchoalveolar lavage samples derived 
      from these patients highlight the potential involvement of the CCR2 pathway in 
      aberrant NK-cell retention at chronic inflammatory sites.
FAU - Hanna, Jacob
AU  - Hanna J
AD  - Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah 
      Medical School, Jerusalem, Israel.
FAU - Mussaffi, Huda
AU  - Mussaffi H
FAU - Steuer, Guy
AU  - Steuer G
FAU - Hanna, Suhair
AU  - Hanna S
FAU - Deeb, Maher
AU  - Deeb M
FAU - Blau, Hannah
AU  - Blau H
FAU - Arnon, Tal I
AU  - Arnon TI
FAU - Weizman, Noam
AU  - Weizman N
FAU - Mandelboim, Ofer
AU  - Mandelboim O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050721
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 3)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (CCL2 protein, human)
RN  - 0 (CCR2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 145892-13-3 (TAP2 protein, human)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
EIN - Blood. 2015 Apr 16;125(16):2583
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 3
MH  - ATP-Binding Cassette Transporters/genetics/*immunology
MH  - Cell Movement/genetics/immunology
MH  - Cells, Cultured
MH  - Chemokine CCL2/immunology
MH  - Chronic Disease
MH  - Gene Expression Regulation/*genetics/immunology
MH  - Genetic Diseases, Inborn/genetics/*immunology/pathology
MH  - Humans
MH  - Inflammation/genetics/immunology/pathology
MH  - Interleukin-12/immunology
MH  - Killer Cells, Natural/*immunology/pathology
MH  - Lymphocyte Activation/genetics/immunology
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/genetics/*immunology
MH  - Respiratory Tract Diseases/genetics/*immunology/pathology
MH  - Signal Transduction/genetics/immunology
MH  - Skin Diseases/genetics/*immunology
EDAT- 2005/07/23 09:00
MHDA- 2005/12/16 09:00
CRDT- 2005/07/23 09:00
PHST- 2005/07/23 09:00 [pubmed]
PHST- 2005/12/16 09:00 [medline]
PHST- 2005/07/23 09:00 [entrez]
AID - S0006-4971(20)68490-7 [pii]
AID - 10.1182/blood-2005-03-0855 [doi]
PST - ppublish
SO  - Blood. 2005 Nov 15;106(10):3465-73. doi: 10.1182/blood-2005-03-0855. Epub 2005 
      Jul 21.