MST1-dependent vesicle trafficking regulates neutrophil transmigration through the vascular basement membrane.

Neutrophils need to penetrate the perivascular basement membrane for successful extravasation into inflamed tissue, but this process is incompletely understood. Recent findings have associated mammalian sterile 20-like kinase 1 (MST1) loss of function with a human primary immunodeficiency disorder, suggesting that MST1 may be involved in immune cell migration. Here, we have shown that MST1 is a critical regulator of neutrophil extravasation during inflammation. Mst1-deficient (Mst1-/-) neutrophils were unable to migrate into inflamed murine cremaster muscle venules, instead persisting between the endothelium and the basement membrane. Mst1-/- neutrophils also failed to extravasate from gastric submucosal vessels in a murine model of Helicobacter pylori infection. Mechanistically, we observed defective translocation of VLA-3, VLA-6, and neutrophil elastase from intracellular vesicles to the surface of Mst1-/- neutrophils, indicating that MST1 is required for this crucial step in neutrophil transmigration. Furthermore, we found that MST1 associates with the Rab27 effector protein synaptotagmin-like protein 1 (JFC1, encoded by Sytl1 in mice), but not Munc13-4, thereby regulating the trafficking of Rab27-positive vesicles to the cellular membrane. Together, these findings highlight a role for MST1 in vesicle trafficking and extravasation in neutrophils, providing an additional mechanistic explanation for the severe immune defect observed in patients with MST1 deficiency.

Posterior cervical foraminotomy: anatomic study in cadavers / Foraminotomia cervical posterior: estudo anatômico em cadáveres / Foraminotoma cervical posterior: estudio anatómico en cadáveres

OBJECTIVE: This study was designed to use different segments of the cervical spine in cadavers to determine how much lateral mass should be resected for adequate foraminal decompression. METHODS: Six cadavers were used. The region of the cervical spine from C1 to the C7-T1 transition was dissected and exposed. The lateral mass of each vertebra was measured bilaterally before the foraminotomy in the following segments: C2-C3, C3-C4, C4-C5, C5-C6 and C6-C7. The procedure was performed with a high-speed drill and through surgical microscopy. Three foraminotomies were performed (F1, F2, F3) in each level. Lateral masses were measured after foraminotomy procedures and compared to the initial measurement, creating a percentage of lateral mass needed for decompression.. The value of the entire surface was defined as 100%. RESULTS: There was a statistical difference between the amounts of the resected lateral mass through each foraminotomy (F1, F2, F3) at the same level. However, there was no statistical significant difference among the different levels. The average percentage of resection of the lateral masses in F2 were 27.7% at C2-C3, 24.8% at C3-C4, 24.4% at C4-C5 and 23.8% and 31.2% at C5-C6 and C6-C7, respectively. In F3, the level that needed greater resection of the lateral masses was C6-C7 level, where the average resection ranged between 41.2% and 47.9%. CONCLUSION: In all segments studied, the removal of approximately 24 to 32% of the facet joint allowed adequate exposure of the foraminal segment, with visualization of the dural sac and the exit of the cervical root. .

OBJETIVO: Utilizar diferentes segmentos da coluna cervical em cadáveres para determinar quanto de massa lateral deve ser ressecada para adequada descompressão foraminal. MÉTODOS: Seis cadáveres foram usados e dissecados de modo a expor a região cervical posterior de C1 até a transição C7-T1. A massa lateral de cada vértebra foi medida bilateralmente antes da foraminotomia nos segmentos: C2-C3, C3-C4, C4-C5, C5-C6 e C6-C7. A foraminotomia foi realizada com "drill" de alta rotação e técnica microscópica. Três foraminotomias foram efetuadas: F1, F2, F3 em cada nível. As massas laterais foram medidas após procedimentos da foraminotomia e comparadas à medida inicial, criando uma porcentagem de massa lateral necessária para descompressão. O valor de cada face articular foi definido como 100%. RESULTADOS: Houve diferença estatística entre a quantidade de massa lateral ressecada entre cada foraminotomia (F1, F2, F3) no mesmo nível. Entretanto, não houve diferença estatística entre as foraminotomias em diferentes níveis. A porcentagem média de ressecção das massas laterais na foraminotomia F2 foi de 27,7% em C2-C3; 24,8% em C3-C4; 24,4% em C4-C5; 23,8% em C5-C6; 31,2% em C6-C7. Na foraminotomia F3, o nível que precisou de maior ressecção das massas laterais foi C6-C7, onde a foraminotomia variou entre 41,2% e 47,9%. CONCLUSÃO: Em todos os segmentos estudados, a remoção de aproximadamente 24 a 32% da articulação facetária permitiu exposição adequada do segmento foraminal com visualização do saco dural e da saída da raiz cervical. .

OBJETIVO: Utilizar diferentes segmentos de la columna cervical en cadáveres para determinar cuánto de masa lateral debe ser resecada para la adecuada descompresión foraminal. MÉTODOS: Seis cadáveres fueron usados y disecados de modo a exponer la región cervical posterior de C1 hasta la transición C7-T1. La masa lateral de cada vértebra fue medida bilateralmente, antes de la foraminotomía, en los segmentos: C2-C3, C3-C4, C4-C5, C5-C6 y C6-C7. La foraminotomía fue realizada con "drill" de alta rotación y técnica microscópica. Se efectuaron tres foraminotomías: F1, F2, F3 en cada nivel. Las masas laterales fueron medidas después de procedimientos de foraminotomía y se compararon con la medida inicial, creando un porcentaje de masa lateral necesaria para descompresión. El valor de cada faz articular fue definido como siendo 100%. RESULTADOS: Hubo diferencia estadística entre la cantidad de masa lateral resecada entre cada foraminotomía (F1, F2, F3) en el mismo nivel. No obstante, no hubo diferencia estadística entre las foraminotomías en niveles diferentes. El porcentaje promedio de resección de las masas laterales, en la foraminotomía F2, fue de 27,7% en C2-C3; 24,8% en C3-C4; 24,4% en C4-C5; 23,8% en C5-C6; 31,2% en C6-C7. En la foraminotomía F3, el nivel que precisó de más resección de las masas laterales fue C6-C7, en el cual la foraminotomía varió entre 41,2% y 47,9%. CONCLUSIÓN: En todos los segmentos estudiados, la remoción de aproximadamente 24 a 32% de la articulación facetaria permitió tener exposición adecuada del segmento foraminal con visualización del saco dural y de la salida de la raíz cervical. .