PMID- 15579451
OWN - NLM
STAT- MEDLINE
DCOM- 20050111
LR  - 20181113
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 165
IP  - 6
DP  - 2004 Dec
TI  - Thrombospondin 2 functions as an endogenous regulator of angiogenesis and 
      inflammation in rheumatoid arthritis.
PG  - 2087-98
AB  - Thrombospondin 2 (TSP2), a matricellular protein with a primary role in 
      modulating cell-matrix interactions, has been implicated in tissue repair and 
      foreign body responses. Here we show that TSP2 has regulatory function in the 
      chronic inflammatory lesions of rheumatoid arthritis. Tissue TSP2, produced by 
      synovial fibroblasts, endothelial cells, and macrophages correlated not only with 
      the intensity of angiogenesis but also with the architecture of lymphoid 
      infiltrates. Synovial tissues with diffuse inflammatory infiltrates had high 
      levels of TSP2, whereas synovial tissues with ectopic germinal center reactions 
      and T cell-B cell aggregates produced low levels. Cell-based gene therapy with 
      TSP2 was used to examine the in vivo effects of the matrix protein on 
      neoangiogenesis and lymphoid organization. Human synovium-severe combined 
      immunodeficiency (SCID) mouse chimeras were treated with TSP2-transfected 
      fibroblasts deposited into the peritoneum. Overexpression of TSP2 led to the 
      accumulation of TSP2 protein in the inflamed synovium and resulted in a prompt 
      inhibition of lesional vascularization. Beside its anti-angiogenic activity, TSP2 
      also suppressed the production of the proinflammatory mediators, interferon-gamma 
      and tumor necrosis factor-alpha, and induced the depletion of tissue-residing T 
      cells. We propose that TSP2 is an endogenous regulator of angiogenesis and 
      autoimmune inflammation in the synovium and represents a protective mechanism 
      preventing ectopic lympho-organogenesis and persistent inflammation in this 
      tissue site.
FAU - Park, Yong Wook
AU  - Park YW
AD  - Department of Medicine, Lowance Center for Human Immunology, Emory University 
      School of Medicine, Atlanta, GA 30322, USA.
FAU - Kang, Young Mo
AU  - Kang YM
FAU - Butterfield, Joe
AU  - Butterfield J
FAU - Detmar, Michael
AU  - Detmar M
FAU - Goronzy, Jorg J
AU  - Goronzy JJ
FAU - Weyand, Cornelia M
AU  - Weyand CM
LA  - eng
GR  - R01 AR 41974/AR/NIAMS NIH HHS/United States
GR  - R01 AI 44142/AI/NIAID NIH HHS/United States
GR  - R01 AR042527/AR/NIAMS NIH HHS/United States
GR  - R01 AI044142/AI/NIAID NIH HHS/United States
GR  - R01 AR041974/AR/NIAMS NIH HHS/United States
GR  - R01 EY 11916/EY/NEI NIH HHS/United States
GR  - R01 AR 42527/AR/NIAMS NIH HHS/United States
GR  - R01 EY011916/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Thrombospondins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (thrombospondin 2)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Arthritis, Rheumatoid/immunology/metabolism/*pathology
MH  - B-Lymphocytes/immunology/metabolism/pathology
MH  - Cells, Cultured
MH  - Endothelial Cells/immunology/metabolism/pathology
MH  - Fibroblasts/immunology/metabolism/pathology
MH  - Inflammation/immunology/metabolism/*pathology
MH  - Interferon-gamma/metabolism
MH  - Macrophages/immunology/metabolism/pathology
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - *Neovascularization, Pathologic
MH  - Peritoneum/immunology/metabolism/pathology
MH  - Synovial Membrane/cytology/immunology/metabolism
MH  - Synovitis/immunology/metabolism/pathology
MH  - T-Lymphocytes/immunology/metabolism/pathology
MH  - Thrombospondins/*pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC1618704
EDAT- 2004/12/08 09:00
MHDA- 2005/01/12 09:00
PMCR- 2005/06/01
CRDT- 2004/12/08 09:00
PHST- 2004/12/08 09:00 [pubmed]
PHST- 2005/01/12 09:00 [medline]
PHST- 2004/12/08 09:00 [entrez]
PHST- 2005/06/01 00:00 [pmc-release]
AID - S0002-9440(10)63259-2 [pii]
AID - 10.1016/S0002-9440(10)63259-2 [doi]
PST - ppublish
SO  - Am J Pathol. 2004 Dec;165(6):2087-98. doi: 10.1016/S0002-9440(10)63259-2.