Objective. Macrophages play a crucial role in health, disease and chronic rejection of transplanted organs. Chronic rejection of transplanted organs remains unresolved issue in organ transplantation. The chronic rejection is the most common cause of graft loss within 10 years of the transplantation. We have recently shown that genetic or pharmacologic interference with the RhoA pathway deregulates the macrophage actin cytoskeleton, causes extreme macrophage elongation and inhibits chronic rejection of mouse cardiac allografts. Because genetic interference is not feasible in humans and RhoA pathway inhibitors are toxic, and so not approved for clinical use, we are seeking to develop a nonpharmacological method to interfere with macrophage phenotype and functions. Methods. We created a permanent rare-earth magnet setup with well-defined magnetic fields and field-gradient patterns. Using Western blotting and immunostaining we investigated the effect of these fields on cultured mouse peritoneal macrophages. Results. The exposure of macrophages to a nonuniform magnetic field causes extreme elongation of macrophages and has a profound effect on their molecular components and organelles. The location and alignment of magnetic-field-elongated macrophages correlates very well with the simulated distribution and orientation of magnetic-force lines. We observed that magnetic force rearranges the macrophage actin cytoskeleton, Golgi complex and cation channel receptor TRPM2 and modifies expression of macrophage molecular markers. We have found that the magnetic field-induced alterations are very similar to changes caused by RhoA interference, which prevented macrophage migration into the transplanted organ. Such a similarity indicates that the magnetic-field-interaction technique has potential, after its further development, to be used to inhibit chronic rejection of transplanted organs.

CITATION INFORMATION: Kloc M., Chen W., Kubiak J., Li X., Ghobrial R., Wosik J. Modification of Macrophage Phenotype by the Magnetic Field Am J Transplant. 2017;17 (suppl 3).

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