AI Article Synopsis
- Proper macrophage migration is essential for effective early responses in the innate immune system, and its misregulation can lead to various health issues.
- The study introduces traction maps of primary human macrophages, revealing that force generation occurs mainly at the leading edge of the cells, influenced by the stiffness of the surrounding matrix.
- Key signaling pathways, including RhoA kinase ROCK, myosin II, and PI3K, are critical for macrophage force generation, while Rac activation via GEF Vav1 is necessary, and Tiam1's involvement is not needed.
Article Abstract
The ability of macrophages to properly migrate is crucial to their success as early responders during the innate immune response. Furthermore, improper regulation of macrophage migration is known to contribute to several pathologies. The signaling mechanisms underlying macrophage migration have been previously studied but to date the mechanical mechanism of macrophage migration has not been determined. In this study, we have created the first traction maps of motile primary human macrophages by observing their migration on compliant polyacrylamide gels. We find that the force generated by migrating macrophages is concentrated in the leading edge of the cell - so-called frontal towing - and that the magnitude of this force is dependent on the stiffness of the underlying matrix. With the aid of chemical inhibitors, we show that signaling through the RhoA kinase ROCK, myosin II, and PI3K is essential for proper macrophage force generation. Finally, we show that Rac activation by its GEF Vav1 is crucial for macrophage force generation while activation through its GEF Tiam1 is unnecessary.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102152 | PMC |
| http://dx.doi.org/10.1039/c4ib00260a | DOI Listing |
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