PMID- 21452319
OWN - NLM
STAT- MEDLINE
DCOM- 20110523
LR  - 20211020
IS  - 1529-0131 (Electronic)
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 63
IP  - 4
DP  - 2011 Apr
TI  - Macrophage migration inhibitory factor regulates neutrophil chemotactic responses 
      in inflammatory arthritis in mice.
PG  - 960-70
LID - 10.1002/art.30203 [doi]
AB  - OBJECTIVE: Macrophage migration inhibitory factor (MIF) facilitates multiple 
      aspects of inflammatory arthritis, the pathogenesis of which has been 
      significantly linked to the activity of neutrophils. The effects of MIF on 
      neutrophil recruitment are unknown. This study was undertaken to investigate the 
      contribution of MIF to the regulation of neutrophil chemotactic responses. 
      METHODS: K/BxN serum-transfer arthritis was induced in wild-type (WT), MIF(-/-) , 
      and monocyte chemotactic protein 1 (MCP-1; CCL2)-deficient mice as well as in WT 
      mice treated with monoclonal antibodies to cytokine-induced neutrophil 
      chemoattractant (anti-KC). Leukocyte trafficking in vivo was examined using 
      intravital microscopy, and neutrophil function in vitro was examined using 
      migration chambers and assessment of MAP kinase activation. RESULTS: K/BxN 
      serum-transfer arthritis was markedly attenuated in MIF(-/-) mice, with 
      reductions in the clinical and histologic severity of arthritis and the synovial 
      expression of KC and interleukin-1. Arthritis was also reduced by anti-KC 
      antibody treatment, but not in MCP-1-deficient mice. In vivo, neutrophil 
      recruitment responses to KC were reduced in MIF(-/-) mice. Similarly, MIF(-/-) 
      mouse neutrophils exhibited reduced chemotactic responses to KC in vitro, despite 
      displaying unaltered chemokine receptor expression. Reduced chemotactic responses 
      of MIF(-/-) mouse neutrophils were associated with reduced phosphorylation of p38 
      and ERK MAP kinases. CONCLUSION: These findings suggest that MIF promotes 
      neutrophil trafficking in inflammatory arthritis via facilitation of 
      chemokine-induced migratory responses and MAP kinase activation. Therapeutic MIF 
      inhibition could limit synovial neutrophil recruitment.
CI  - Copyright (c) 2011 by the American College of Rheumatology.
FAU - Santos, Leilani L
AU  - Santos LL
AD  - Monash Medical Centre, Clayton, Victoria, Australia.
FAU - Fan, Huapeng
AU  - Fan H
FAU - Hall, Pam
AU  - Hall P
FAU - Ngo, Devi
AU  - Ngo D
FAU - Mackay, Charles R
AU  - Mackay CR
FAU - Fingerle-Rowson, Gunter
AU  - Fingerle-Rowson G
FAU - Bucala, Richard
AU  - Bucala R
FAU - Hickey, Michael J
AU  - Hickey MJ
FAU - Morand, Eric F
AU  - Morand EF
LA  - eng
GR  - R01 AR050498/AR/NIAMS NIH HHS/United States
GR  - R01-AR-50498/AR/NIAMS NIH HHS/United States
GR  - R01 AR049610/AR/NIAMS NIH HHS/United States
GR  - R01-AR5-1807-01/AR/NIAMS NIH HHS/United States
GR  - R01 AR051807/AR/NIAMS NIH HHS/United States
GR  - R01 AR051807-01/AR/NIAMS 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 (Chemokine CXCL1)
RN  - 0 (Cxcl1 protein, mouse)
RN  - 0 (Macrophage Migration-Inhibitory Factors)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Adaptive Immunity/physiology
MH  - Animals
MH  - Arthritis, Experimental/pathology/*physiopathology
MH  - Cell Movement/drug effects
MH  - Chemokine CXCL1/pharmacology
MH  - Chemotaxis, Leukocyte/drug effects/*physiology
MH  - Disease Models, Animal
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Macrophage Migration-Inhibitory Factors/deficiency/genetics/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neutrophils/drug effects/*pathology
PMC - PMC3069137
MID - NIHMS258341
EDAT- 2011/04/01 06:00
MHDA- 2011/05/24 06:00
PMCR- 2012/04/01
CRDT- 2011/04/01 06:00
PHST- 2011/04/01 06:00 [entrez]
PHST- 2011/04/01 06:00 [pubmed]
PHST- 2011/05/24 06:00 [medline]
PHST- 2012/04/01 00:00 [pmc-release]
AID - 10.1002/art.30203 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2011 Apr;63(4):960-70. doi: 10.1002/art.30203.