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Mactinin: a modulator of the monocyte response to inflammation
Sharon D Luikart1, Hollis E Krug, Robert D Nelson
1Department of Medicine, Veterans Affairs Medical Center and University of Minnesota, Minneapolis, Minnesota, USA. sharon.luikart@med.va.gov
Abstract:
During inflammatory processes, monocytes leave the blood stream at increased rates and enter inflammation tissue, where they undergo phenotypic transformation to mature macrophages with enhanced phagocytic activity. alpha-Actinin, a cytoskeletal protein, is present in focal adhesion complexes and left in the microenvironment as a result of cell movement. Mactinin, a 31 kDa amino-terminal fragment of alpha-actinin, is generated by the degradation of extracellular alpha-actinin by monocyte-secreted urokinase. We have previously demonstrated that mactinin promotes monocyte/macrophage maturation. We now report that 0.5-10 nM mactinin has significant chemotactic activity for monocytes. Mactinin seems to be present in inflammatory arthritis synovial fluid, because affinity-purified antisera reacted with a protein of the expected molecular mass in various types of arthritis fluids that were immunoaffinity-purified and subjected to Western analysis. Thus, six of seven samples from patients with psoriatic arthritis, reactive arthritis, gout, or ankylosing spondylitis contained mactinin at levels that are active in vitro. Initially, mactinin was not found in affinity-purified rheumatoid arthritis samples. However, it was detectable after the dissociation of immune complexes, suggesting that it was complexed to anti-microfilament auto-antibodies. In addition, mactinin was found in the lavage fluid from the arthritic knee joints of rabbits with antigen-induced arthritis and was absent from the contralateral control knee fluids. We conclude that mactinin is present in several types of inflammatory arthritis and might modulate mononuclear phagocyte response to inflammation.
Insights
Mactinin, a fragment of alpha-actinin, attracts monocytes and is found in inflammatory arthritis fluids. This protein may influence the immune cell response in inflammatory conditions like arthritis.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Monocytes transform into macrophages during inflammation, enhancing phagocytic activity.
- Alpha-actinin is a cytoskeletal protein involved in cell adhesion and movement.
- Mactinin, an alpha-actinin fragment, promotes monocyte/macrophage maturation.
Purpose of the Study:
- To investigate the chemotactic activity of mactinin on monocytes.
- To determine the presence and levels of mactinin in inflammatory arthritis synovial fluid.
- To explore mactinin's potential role in modulating mononuclear phagocyte responses in arthritis.
Main Methods:
- Chemotaxis assays were performed using varying concentrations of mactinin (0.5-10 nM).
- Immunoaffinity purification and Western blot analysis were used to detect mactinin in human arthritis synovial fluid.
- Mactinin presence was also assessed in rabbit knee joint lavage fluid from antigen-induced arthritis models.
Main Results:
- Mactinin demonstrated significant chemotactic activity for monocytes at concentrations of 0.5-10 nM.
- Mactinin was detected in synovial fluid from patients with psoriatic arthritis, reactive arthritis, gout, and ankylosing spondylitis.
- Mactinin was found in rabbit arthritis lavage fluid but not in control contralateral knee fluids; it was also detected in rheumatoid arthritis samples after immune complex dissociation.
Conclusions:
- Mactinin is present in various forms of inflammatory arthritis.
- Mactinin exhibits chemotactic properties for monocytes, suggesting a role in recruiting these cells to inflammatory sites.
- Mactinin may play a role in regulating mononuclear phagocyte responses during inflammatory arthritis.