Differences in the cell morphology of macrophages in either pro-inflammatory (M1)-polarizing or pro-healing (M2)-polarizing conditions have been previously observed. As described in this study, M1-polarizing stimuli (LPS plus IFNγ) cause cells to flatten into a round, pancake-like shape, whereas M2-polarizing stimuli (IL-4 and IL-13) induce an elongated cell shape. The extent of cell elongation was shown to correlate with the expression levels of the M2 phenotype marker arginase 1. Using engineered cell culture substrates to control cell shape, the authors found that cell elongation itself promotes macrophage polarization towards the M2 phenotype. Elongation of cells enhanced cytokine-induced M2 polarization and reduced the expression of induced nitric oxide synthase in response to M1-polarizing stimuli. Although cell elongation itself was not affected, inhibition of cytoskeletal contractility abrogated the upregulation of arginase 1 expression by cells elongated on the substrates but not in cytokine-polarized M2 macrophages. Together, these data indicate that cell shape has an important role in modulating M2 macrophage polarization.
References
McWhorter, F. Y. et al. Modulation of macrophage phenotype by cell shape. Proc. Natl Acad. Sci. USA http://dx.doi.org/10.1073/pnas.1308887110 (2013)
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Leavy, O. The shape of things to come. Nat Rev Immunol 13, 775 (2013). https://doi.org/10.1038/nri3559
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DOI: https://doi.org/10.1038/nri3559