PMID- 22914861
OWN - NLM
STAT- MEDLINE
DCOM- 20130118
LR  - 20161125
IS  - 1460-2377 (Electronic)
IS  - 0953-8178 (Linking)
VI  - 24
IP  - 9
DP  - 2012 Sep
TI  - Syk-dependent signaling pathways in neutrophils and macrophages are indispensable 
      in the pathogenesis of anti-collagen antibody-induced arthritis.
PG  - 539-50
LID - 10.1093/intimm/dxs078 [doi]
AB  - Spleen tyrosine kinase (Syk) is associated with Fcgamma receptors (FcgammaRs) and 
      transmits activation signals through FcgammaRs in myeloid cells. Thus, application of 
      drugs to inhibit Syk activity can affect the development of immune diseases 
      mediated by autoantibodies, while unexpected systemic effects by the inhibition 
      may be concerned because Syk has multiple physiological functions. We used 
      tamoxifen-inducible systemic conditional Syk knockout (KO) mice to evaluate the 
      role of Syk in the pathogenesis of autoimmune arthritis and to investigate the 
      systemic effects of Syk deletion. In a collagen antibody-induced arthritis model, 
      Syk KO mice were almost completely protected from disease induction and showed 
      significantly attenuated accumulation of neutrophils and macrophages in the 
      joints. Syk-deleted macrophages showed less IL-6 and MCP-1 production upon FcgammaR 
      ligation and exhibited reduced FcgammaR-mediated phagocytosis in vitro. Syk-deleted 
      macrophages produce more RANTES upon FcgammaR ligation, indicating a Syk-independent 
      signaling through the FcgammaR. We further found that both wild-type and Syk-deleted 
      macrophages induced neutrophil chemotaxis upon FcgammaR ligation in vitro, and 
      air-pouch model demonstrated that Syk-deleted neutrophils have a potential to 
      infiltrate into local tissues in response to collagen and anti-collagen 
      antibodies. However, Syk-deleted neutrophils exhibited greatly decreased 
      neutrophil extracellular traps formation and FcgammaR-mediated phagocytosis. Our 
      results indicated that Syk deficiency rendered mice completely unresponsive to 
      immune activation by anti-collagen antibodies with disabling one pathway of 
      FcgammaR-mediated signaling that was crucial for arthritis induction.
FAU - Ozaki, Naoko
AU  - Ozaki N
AD  - Department of Molecular & Cellular Biology, Kobe Pharma Research Institute, 
      Nippon Boehringer Ingelheim Co., Ltd, Hyogo, Japan.
FAU - Suzuki, Shinobu
AU  - Suzuki S
FAU - Ishida, Masato
AU  - Ishida M
FAU - Harada, Yasuyo
AU  - Harada Y
FAU - Tanaka, Kohji
AU  - Tanaka K
FAU - Sato, Yayoi
AU  - Sato Y
FAU - Kono, Takeshi
AU  - Kono T
FAU - Kubo, Masato
AU  - Kubo M
FAU - Kitamura, Daisuke
AU  - Kitamura D
FAU - Encinas, Jeffrey
AU  - Encinas J
FAU - Hara, Hiromitsu
AU  - Hara H
FAU - Yoshida, Hiroki
AU  - Yoshida H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Int Immunol
JT  - International immunology
JID - 8916182
RN  - 0 (Autoantibodies)
RN  - 0 (Cytokines)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Receptors, IgG)
RN  - 9007-34-5 (Collagen)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (SYK protein, human)
RN  - EC 2.7.10.2 (Syk Kinase)
RN  - EC 2.7.10.2 (Syk protein, mouse)
SB  - IM
MH  - Animals
MH  - Arthritis, Experimental/*immunology
MH  - Autoantibodies/immunology/*metabolism
MH  - Cell Movement/genetics/immunology
MH  - Cells, Cultured
MH  - Collagen/immunology
MH  - Cytokines/genetics/metabolism
MH  - Gene Expression Regulation
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - Macrophages/drug effects/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neutrophils/drug effects/*immunology
MH  - Phagocytosis
MH  - Protein-Tyrosine Kinases/genetics/*metabolism
MH  - Receptors, IgG/metabolism
MH  - Signal Transduction/genetics/immunology
MH  - Syk Kinase
EDAT- 2012/08/24 06:00
MHDA- 2013/01/19 06:00
CRDT- 2012/08/24 06:00
PHST- 2012/08/24 06:00 [entrez]
PHST- 2012/08/24 06:00 [pubmed]
PHST- 2013/01/19 06:00 [medline]
AID - dxs078 [pii]
AID - 10.1093/intimm/dxs078 [doi]
PST - ppublish
SO  - Int Immunol. 2012 Sep;24(9):539-50. doi: 10.1093/intimm/dxs078.