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Updated: Jun 3, 2026
Detecting Migration and Infiltration of Neutrophils in Mice
Published on: February 6, 2020
Macrophage migration inhibitory factor regulates neutrophil chemotactic responses in inflammatory arthritis in mice
Leilani L Santos1, Huapeng Fan, Pam Hall
1Monash Medical Centre, Clayton, Victoria, Australia.
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.
Insights
Macrophage migration inhibitory factor (MIF) reduces neutrophil recruitment in inflammatory arthritis by enhancing chemokine responses and MAP kinase activation. Inhibiting MIF may limit neutrophil infiltration in joints.
Area of Science:
- Immunology
- Rheumatology
- Cell Biology
Background:
- Macrophage migration inhibitory factor (MIF) plays a role in inflammatory arthritis.
- Neutrophil activity is critical in inflammatory arthritis pathogenesis.
- The specific role of MIF in neutrophil recruitment remains unclear.
Purpose of the Study:
- To investigate the contribution of MIF to neutrophil chemotactic responses.
- To understand how MIF regulates neutrophil migration in inflammatory arthritis.
Main Methods:
- K/BxN serum-transfer arthritis induced in wild-type, MIF-deficient, and MCP-1-deficient mice.
- Leukocyte trafficking examined using intravital microscopy.
- Neutrophil function assessed in vitro via migration chambers and MAP kinase activation assays.
Main Results:
- MIF-deficient mice showed significantly reduced arthritis severity and synovial expression of KC and IL-1.
- Neutrophil recruitment to KC was impaired in MIF-deficient mice, both in vivo and in vitro.
- Reduced neutrophil chemotaxis in MIF-deficient mice correlated with decreased p38 and ERK MAP kinase phosphorylation.
Conclusions:
- MIF promotes neutrophil trafficking in inflammatory arthritis by enhancing chemokine-induced migration and MAP kinase activation.
- Therapeutic targeting of MIF could be a strategy to reduce synovial neutrophil recruitment in inflammatory arthritis.
