PMID- 12794168
OWN - NLM
STAT- MEDLINE
DCOM- 20030908
LR  - 20220419
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 170
IP  - 12
DP  - 2003 Jun 15
TI  - Immunoglobulin activation of T cell chemoattractant expression in fibroblasts 
      from patients with Graves' disease is mediated through the insulin-like growth 
      factor I receptor pathway.
PG  - 6348-54
AB  - Graves' disease (GD) is associated with T cell infiltration, but the mechanism 
      for lymphocyte trafficking has remained uncertain. We reported previously that 
      fibroblasts from patients with GD express IL-16, a CD4-specific chemoattractant, 
      and RANTES, a C-C chemokine, in response to GD-specific IgG (GD-IgG). We 
      unexpectedly found that these responses result from a functional interaction 
      between GD-IgG and the insulin-like growth factor (IGF)-I receptor (IGF-IR). 
      IGF-I and the IGF-IR-specific IGF-I analog, des(1-3), mimic the effects of 
      GD-IgG. Neither GD-IgG nor IGF-I activates chemoattractant expression in control 
      fibroblasts from donors without GD. Interrupting IGF-IR function with specific 
      receptor-blocking Abs or by transiently transfecting fibroblasts with a dominant 
      negative mutant IGF-IR completely attenuates signaling provoked by GD-IgG. 
      Moreover, GD-IgG displaces specific (125)I-labeled IGF-I binding to fibroblasts 
      and attenuates IGF-IR detection by flow cytometry. These findings identify a 
      novel disease mechanism involving a functional GD-IgG/IGF-IR bridge, which 
      potentially explains T cell infiltration in GD. Interrupting this pathway may 
      constitute a specific therapeutic strategy.
FAU - Pritchard, Jane
AU  - Pritchard J
AD  - Division of Molecular Medicine, Department of Medicine, Harbor-University of 
      California Los Angeles Medical Center, Torrance, CA 90502, USA.
FAU - Han, Rui
AU  - Han R
FAU - Horst, Noah
AU  - Horst N
FAU - Cruikshank, William W
AU  - Cruikshank WW
FAU - Smith, Terry J
AU  - Smith TJ
LA  - eng
GR  - EY08976/EY/NEI NIH HHS/United States
GR  - EY11708/EY/NEI NIH HHS/United States
GR  - HL32902/HL/NHLBI NIH HHS/United States
GR  - MO1RR00425/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Autoantigens)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Interleukin-16)
RN  - 0 (Iodine Radioisotopes)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
SB  - IM
MH  - Adjuvants, Immunologic/biosynthesis/genetics/metabolism/physiology
MH  - Autoantigens/biosynthesis/genetics/metabolism/physiology
MH  - Cell Movement/immunology
MH  - Cells, Cultured
MH  - Chemokine CCL5/*biosynthesis/physiology
MH  - Chemotaxis, Leukocyte/genetics/immunology
MH  - Fibroblasts/*immunology/metabolism/pathology
MH  - Graves Disease/*immunology/pathology
MH  - Humans
MH  - Immunoglobulin G/metabolism/*pharmacology
MH  - Interleukin-16/*biosynthesis/physiology
MH  - Iodine Radioisotopes/metabolism
MH  - Protein Binding/immunology
MH  - Receptor, IGF Type 1/biosynthesis/genetics/metabolism/*physiology
MH  - Signal Transduction/*immunology
MH  - T-Lymphocytes/cytology/*immunology
MH  - Transfection
EDAT- 2003/06/10 05:00
MHDA- 2003/09/10 05:00
CRDT- 2003/06/10 05:00
PHST- 2003/06/10 05:00 [pubmed]
PHST- 2003/09/10 05:00 [medline]
PHST- 2003/06/10 05:00 [entrez]
AID - 10.4049/jimmunol.170.12.6348 [doi]
PST - ppublish
SO  - J Immunol. 2003 Jun 15;170(12):6348-54. doi: 10.4049/jimmunol.170.12.6348.