In Vivo Morphometric Analysis of Human Cranial Nerves Using Magnetic Resonance Imaging in Meniere's Disease Ears and Normal Hearing Ears

Zehrer, Annette; Pick, Robert; Salvermoser, Melanie; Boda, Annegret; Miller, Meike; Stark, Konstantin; Weckbach, Ludwig T.; Walzog, Barbara und Begandt, Daniela (2018): In Vivo Morphometric Analysis of Human Cranial Nerves Using Magnetic Resonance Imaging in Meniere's Disease Ears and Normal Hearing Ears. In: Journal of Immunology, Bd. 201, Nr. 6: S. 1748-1764

Abstract

Neutrophils are the first leukocytes to arrive at sites of injury during the acute inflammatory response. To maintain the polarized morphology during migration, nonmuscle myosins class II are essential, but studies using genetic models to investigate the role of Myh9 for neutrophil migration were missing. In this study, we analyzed the functional role of Myh9 on neutrophil trafficking using genetic down-regulation of Myh9 in Vav-iCre(+)/Myh9(wt/fl) mice because the complete knockout of Myh9 in the hematopoietic system was lethal. Migration velocity and Euclidean distance were significantly diminished during mechanotactic migration of Vav-iCre(+)/Myh9(wt/fl) neutrophils compared with Vav-iCre(-)/Myh9(wt/fl) control neutrophils. Similar results were obtained for transmigration and migration in confined three-dimensional environments. Stimulated emission depletion nanoscopy revealed that a certain threshold of Myh9 was required to maintain proper F-actin dynamics in the front of the migrating cell. In laser-induced skin injury and in acute peritonitis, reduced Myh9 expression in the hematopoietic system resulted in significantly diminished neutrophil extravasation. Investigation of bone marrow chimeric mice in the peritonitis model revealed that the migration defect was cell intrinsic. Expression of Myh9-EGFP rescued the Myh9-related defects in two-dimensional and three-dimensional migration of Hoxb8-SCF cell-derived neutrophils generated from fetal liver cells with a Myh9 knockdown. Live cell imaging provided evidence that Myh9 was localized in branching lamellipodia and in the uropod where it may enable fast neutrophil migration. In summary, the severe migration defects indicate an essential and fundamental role of Myh9 for neutrophil trafficking in innate immunity.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0022-1767
• Sprache: Englisch