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Perivascular Mast Cells Govern Shear Stress-Induced Arteriogenesis by Orchestrating Leukocyte Function

The body has the capacity to compensate for an occluded artery by creating a natural bypass upon increased fluid shear stress. How this mechanical force is translated into collateral artery growth (arteriogenesis) is unresolved. We show that extravasation of neutrophils mediated by the platelet rece...

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Bibliographic Details
Published in:Cell reports (Cambridge) 2016-08, Vol.16 (8), p.2197-2207
Main Authors: Chillo, Omary, Kleinert, Eike Christian, Lautz, Thomas, Lasch, Manuel, Pagel, Judith-Irina, Heun, Yvonn, Troidl, Kerstin, Fischer, Silvia, Caballero-Martinez, Amelia, Mauer, Annika, Kurz, Angela R.M., Assmann, Gerald, Rehberg, Markus, Kanse, Sandip M., Nieswandt, Bernhard, Walzog, Barbara, Reichel, Christoph A., Mannell, Hanna, Preissner, Klaus T., Deindl, Elisabeth
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Language:English
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Summary:The body has the capacity to compensate for an occluded artery by creating a natural bypass upon increased fluid shear stress. How this mechanical force is translated into collateral artery growth (arteriogenesis) is unresolved. We show that extravasation of neutrophils mediated by the platelet receptor GPIbα and uPA results in Nox2-derived reactive oxygen radicals, which activate perivascular mast cells. These c-kit+/CXCR-4+ cells stimulate arteriogenesis by recruiting additional neutrophils as well as growth-promoting monocytes and T cells. Additionally, mast cells may directly contribute to vascular remodeling and vascular cell proliferation through increased MMP activity and by supplying growth-promoting factors. Boosting mast cell recruitment and activation effectively promotes arteriogenesis, thereby protecting tissue from severe ischemic damage. We thus find that perivascular mast cells are central regulators of shear stress-induced arteriogenesis by orchestrating leukocyte function and growth factor/cytokine release, thus providing a therapeutic target for treatment of vascular occlusive diseases. [Display omitted] •Arteriogenesis is mediated by coordinated action of innate immune cells•Mast cells orchestrate leukocyte function in arteriogenesis•Platelet GPIbα is decisive for shear stress-provoked mast cell activation•Shear stress-induced mast cell activation is mediated by neutrophil-derived ROS Increased fluid shear stress is the triggering force for the growth of natural bypasses. How this mechanical load is translated into collateral artery growth is an enigma. Chillo et al. find that mast cell activation governs arteriogenesis by orchestrating leukocyte function.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2016.07.040