PMID- 20191628
OWN - NLM
STAT- MEDLINE
DCOM- 20100402
LR  - 20211020
IS  - 1529-0131 (Electronic)
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 62
IP  - 3
DP  - 2010 Mar
TI  - Neutrophils in a mouse model of autoantibody-mediated arthritis: critical 
      producers of Fc receptor gamma, the receptor for C5a, and lymphocyte 
      function-associated antigen 1.
PG  - 753-64
LID - 10.1002/art.27238 [doi]
AB  - OBJECTIVE: Neutrophils represent a prominent component of inflammatory joint 
      effusions and are required for synovial inflammation in mouse models, but the 
      mechanisms are poorly understood. In this study, we developed a system with which 
      to test the importance of the production of specific factors by neutrophils in a 
      mouse model of arthritis. METHODS: Neutrophil-deficient Gfi-1(-/-) mice were 
      administered sublethal doses of radiation and were then engrafted with donor bone 
      marrow cells (BMCs), which resulted in the production of mature neutrophils 
      within 2 weeks. By reconstituting with BMCs from mice lacking selected 
      proinflammatory factors, we generated mice that specifically lacked these factors 
      on their neutrophils. Arthritis was initiated by transfer of K/BxN serum to 
      identify the role of defined neutrophil factors on the incidence and severity of 
      arthritis. RESULTS: Neutrophils lacking the signaling chain of stimulatory Fc 
      receptors (FcRgamma(-/-)) were unable to elicit arthritis, but neutrophils 
      lacking FcgammaRIII still did so. Neutrophils lacking the chemotactic or adhesion 
      receptor C5a receptor (C5aR) or CD11a/lymphocyte function-associated antigen 1 
      (LFA-1) also failed to initiate arthritis but could enter joints in which 
      inflammation had been initiated by wild-type neutrophils. Neutrophils unable to 
      produce interleukin-1alpha (IL-1alpha) and IL-1beta (IL-1alpha/beta(-/-)) or 
      leukotrienes (5-lipoxygenase [5-LOX(-/-)]) produced arthritis of intermediate 
      severity. The inability of neutrophils to make tumor necrosis factor or to 
      express receptors for tumor necrosis factor or IL-1 had no effect on arthritis. 
      CONCLUSION: A novel transfer system was developed to identify neutrophil 
      production of FcRgamma, C5aR, and CD11a/LFA-1 as critical components of 
      autoantibody-mediated arthritis. Neutrophil production of IL-1 and leukotriene 
      B(4) likely contributes to inflammation but is not essential. Molecular 
      requirements for neutrophil influx into joints become more permissive after 
      inflammation is initiated.
FAU - Monach, Paul A
AU  - Monach PA
AD  - Joslin Diabetes Center, Brigham and Women's Hospital, and Harvard Medical School, 
      Boston, MA 02115, USA.
FAU - Nigrovic, Peter A
AU  - Nigrovic PA
FAU - Chen, Mei
AU  - Chen M
FAU - Hock, Hanno
AU  - Hock H
FAU - Lee, David M
AU  - Lee DM
FAU - Benoist, Christophe
AU  - Benoist C
FAU - Mathis, Diane
AU  - Mathis D
LA  - eng
GR  - R01-AR-46580/AR/NIAMS NIH HHS/United States
GR  - R01-AR-055271/AR/NIAMS NIH HHS/United States
GR  - RC2 GM093080-01/GM/NIGMS NIH HHS/United States
GR  - RC2 GM093080/GM/NIGMS NIH HHS/United States
GR  - R01 AR046580/AR/NIAMS NIH HHS/United States
GR  - P01 AI065858/AI/NIAID NIH HHS/United States
GR  - P01-AI-65858/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Autoantibodies)
RN  - 0 (Interleukin-1alpha)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Leukotrienes)
RN  - 0 (Lymphocyte Function-Associated Antigen-1)
RN  - 0 (Receptor, Anaphylatoxin C5a)
RN  - 0 (Receptors, IgG)
SB  - IM
MH  - Animals
MH  - Arthritis, Experimental/etiology/immunology/metabolism
MH  - Autoantibodies/immunology
MH  - Autoimmune Diseases
MH  - Bone Marrow Transplantation
MH  - Flow Cytometry
MH  - Interleukin-1alpha/biosynthesis
MH  - Interleukin-1beta/biosynthesis
MH  - Leukotrienes/biosynthesis
MH  - Lymphocyte Function-Associated Antigen-1/*biosynthesis
MH  - Mice
MH  - Neutrophils/metabolism/*physiology
MH  - Receptor, Anaphylatoxin C5a/*biosynthesis
MH  - Receptors, IgG/*biosynthesis
PMC - PMC3057458
MID - NIHMS190574
EDAT- 2010/03/02 06:00
MHDA- 2010/04/03 06:00
PMCR- 2011/03/15
CRDT- 2010/03/02 06:00
PHST- 2010/03/02 06:00 [entrez]
PHST- 2010/03/02 06:00 [pubmed]
PHST- 2010/04/03 06:00 [medline]
PHST- 2011/03/15 00:00 [pmc-release]
AID - 10.1002/art.27238 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2010 Mar;62(3):753-64. doi: 10.1002/art.27238.