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Actin dynamics in the regulation of endothelial barrier functions and neutrophil recruitment during endotoxemia and sepsis

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Abstract

Sepsis is a leading cause of death worldwide. Increased vascular permeability is a major hallmark of sepsis. Dynamic alterations in actin fiber formation play an important role in the regulation of endothelial barrier functions and thus vascular permeability. Endothelial integrity requires a delicate balance between the formation of cortical actin filaments that maintain endothelial cell contact stability and the formation of actin stress fibers that generate pulling forces, and thus compromise endothelial cell contact stability. Current research has revealed multiple molecular pathways that regulate actin dynamics and endothelial barrier dysfunction during sepsis. These include intracellular signaling proteins of the small GTPases family (e.g., Rap1, RhoA and Rac1) as well as the molecules that are directly acting on the actomyosin cytoskeleton such as myosin light chain kinase and Rho kinases. Another hallmark of sepsis is an excessive recruitment of neutrophils that also involves changes in the actin cytoskeleton in both endothelial cells and neutrophils. This review focuses on the available evidence about molecules that control actin dynamics and regulate endothelial barrier functions and neutrophil recruitment. We also discuss treatment strategies using pharmaceutical enzyme inhibitors to target excessive vascular permeability and leukocyte recruitment in septic patients.

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Acknowledgements

This work was supported by an international bilateral grant from the Mexican Council for Science and Technology (Conacyt, 207268 to MS) and the German Ministry for Education and Research (BMBF, 01DN14039 to AZ).

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Authors and Affiliations

  1. Department for Molecular Biomedicine, Centre for Investigation and Advanced Studies of the National Polytechnic Institute (Cinvestav-IPN), Av. IPN 2508, San Pedro Zacatenco, GAM, 07360, Mexico City, Mexico

    Michael Schnoor, Alexander García Ponce & Eduardo Vadillo

  2. Oncology Research Unit, National Medical Center, Mexican Institute for Social Security, 06720, Mexico City, Mexico

    Rosana Pelayo

  3. Department of Anaesthesiology, Critical Care and Pain Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, 48149, Münster, Germany

    Jan Rossaint & Alexander Zarbock

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  1. Michael Schnoor
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  2. Alexander García Ponce
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  3. Eduardo Vadillo
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Schnoor, M., García Ponce, A., Vadillo, E. et al. Actin dynamics in the regulation of endothelial barrier functions and neutrophil recruitment during endotoxemia and sepsis. Cell. Mol. Life Sci. 74, 1985–1997 (2017). https://doi.org/10.1007/s00018-016-2449-x

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  • DOI: https://doi.org/10.1007/s00018-016-2449-x

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