Macrophage polarization impacts tunneling nanotube formation and intercellular organelle trafficking

摘要: Tunneling nanotubes (TNTs) are cellular extensions enabling cytosol-to-cytosol intercellular interaction between numerous cell types including macrophages. Previous studies of hematopoietic stem and progenitor (HSPC) transplantation for the lysosomal storage disorder cystinosis have shown that HSPC-derived macrophages form TNTs to deliver cystinosin-bearing lysosomes cystinotic cells, leading tissue preservation. Here, we explored if macrophage polarization either proinflammatory M1-like M(LPS/IFNγ) or anti-inflammatory M2-like M(IL-4/IL-10) affected TNT-like protrusion formation, transport and, ultimately, efficacy prevention. We designed new automated image processing algorithms used demonstrate LPS/IFNγ decreased bone marrow-derived (BMDMs) formation protrusions, some which displayed characteristics TNTs, cytoskeletal structure, 3D morphology size. In contrast, co-culture with fibroblasts yielded more frequent larger as well increased mitochondrial trafficking diseased fibroblasts. Unexpectedly, observed normal therapeutic following disruption IL-4/IL-10 in vivo by HSPCs isolated from Rac2-/- mouse model. Altogether, developed unbiased quantification systems probe mechanistic aspects TNT function vitro, while HSPC into mice provides a complex disease While differences culture models exemplify oversimplicity vitro cytokine treatment, they simultaneously utility our model recapitulates phenomenon cells stimulating thicker Ultimately, can use both approaches expand protrusions delivery system regenerative medicine.