Proc Natl Acad Sci U S A. 2019 Dec 6;116(52):26752-26758. doi: 10.1073/pnas.1902502116. | PubMed

Eduardo Vadillo¹, Sandra Chánez-Paredes¹, Hilda Vargas-Robles¹, Idaira María Guerrero-Fonseca¹, Ramón Castellanos-Martínez¹, Alexander García-Ponce¹, Porfirio Nava², Daniel Alberto Girón-Pérez¹, Leopoldo Santos-Argumedo¹, Michael Schnoor³

1. Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), San Pedro Zacatenco, 07360 Mexico City, Mexico.
2. Department of Physiology, Biophysics and Neurosciences, CINVESTAV-IPN, San Pedro Zacatenco, 07360 Mexico City, Mexico.
3. Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), San Pedro Zacatenco, 07360 Mexico City, Mexico; mschnoor@cinvestav.mx.

Abstract

Neutrophil extravasation is a migratory event in response to inflammation that depends on cytoskeletal dynamics regulated by myosins. Myosin-1e (Myo1e) is a long-tailed class-I myosin that has not yet been studied in the context of neutrophil-endothelial interactions and neutrophil extravasation. Intravital microscopy of TNFα-inflamed cremaster muscles in Myo1e-deficient mice revealed that Myo1e is required for efficient neutrophil extravasation. Specifically, Myo1e deficiency caused increased rolling velocity, decreased firm adhesion, aberrant crawling, and strongly reduced transmigration. Interestingly, we observed a striking discontinuous rolling behavior termed "intermittent rolling," during which Myo1e-deficient neutrophils showed alternating rolling and jumping movements. Surprisingly, chimeric mice revealed that these effects were due to Myo1e deficiency in leukocytes. Vascular permeability was not significantly altered in Myo1e KO mice. Myo1e-deficient neutrophils showed diminished arrest, spreading, uropod formation, and chemotaxis due to defective actin polymerization and integrin activation. In conclusion, Myo1e critically regulates adhesive interactions of neutrophils with the vascular endothelium and neutrophil extravasation. Myo1e may therefore be an interesting target in chronic inflammatory diseases characterized by excessive neutrophil recruitment.

Presented By Eduardo Vadillo