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Migration inhibition factor-like activity in inflammatory synovial fluids might be due to proteases
Abstract:
Using an assay of macrophage migration, where the cells emigrate from an agarose droplet, it was found that the neutral proteases trypsin, chymotrypsin, Pronase and elastase have MIF-like activity. Appropriate enzyme inhibitors counteract this effect. To twelve synovial fluids from patients with inflammatory arthritis, which have MIF-like activity (migration index between 0-3 and 0-7) protease indhibitors (Trasylol, ovomucoid and soybean inhibitor) were added. Ten of the fluids lost some of their MIF-like activity with at least one inhibitor. Phenylmethylsulphonylfluoride counteracted totally the MIF-like activity of the two fluids tested. It is concluded that MIF-like activity of inflammatory synovial fluids is due, at least partially, to proteases.
Insights
Neutral proteases like trypsin exhibit macrophage migration inhibition factor (MIF)-like activity. Protease inhibitors reduced this activity in inflammatory arthritis synovial fluids, suggesting proteases contribute to MIF-like effects.
Area of Science:
- Biochemistry
- Immunology
- Cell Biology
Background:
- Macrophage migration inhibition factor (MIF) plays a crucial role in inflammatory arthritis.
- The precise molecular mechanisms underlying MIF-like activity in synovial fluid are not fully understood.
Purpose of the Study:
- To investigate the role of neutral proteases in the macrophage migration inhibition factor (MIF)-like activity observed in inflammatory arthritis synovial fluids.
Main Methods:
- Macrophage migration assays were performed using agarose droplets.
- The effects of specific neutral proteases (trypsin, chymotrypsin, Pronase, elastase) on macrophage migration were assessed.
- The impact of various protease inhibitors (Trasylol, ovomucoid, soybean inhibitor, phenylmethylsulphonylfluoride) on MIF-like activity in synovial fluid was evaluated.
Main Results:
- Neutral proteases demonstrated significant MIF-like activity in vitro.
- Protease inhibitors effectively counteracted the MIF-like activity induced by these enzymes.
- In ten out of twelve inflammatory arthritis synovial fluid samples, protease inhibitors partially or fully abolished the observed MIF-like activity.
Conclusions:
- Proteases are identified as a significant contributor to the MIF-like activity found in synovial fluids from patients with inflammatory arthritis.
- Targeting these proteases may offer a therapeutic strategy for managing inflammatory conditions.