Endothelial Plasmalemma Vesicle-Associated Protein Regulates the Homeostasis of Splenic Immature B Cells and B-1 B Cells.

Plasmalemma vesicle-associated protein (Plvap) is an endothelial protein with roles in endothelial diaphragm formation and maintenance of basal vascular permeability. At the same time, Plvap has roles in immunity by facilitating leukocyte diapedesis at inflammatory sites and controlling peripheral lymph node morphogenesis and the entry of soluble Ags into lymph node conduits. Based on its postulated role in diapedesis, we have investigated the role of Plvap in hematopoiesis and show that deletion of Plvap results in a dramatic decrease of IgM+IgDlo B cells in both the spleen and the peritoneal cavity. Tissue-specific deletion of Plvap demonstrates that the defect is B cell extrinsic, because B cell and pan-hematopoietic Plvap deletion has no effect on IgM+IgDlo B cell numbers. Endothelial-specific deletion of Plvap in the embryo or at adult stage recapitulates the full Plvap knockout phenotype, whereas endothelial-specific reconstitution of Plvap under the Chd5 promoter rescues the IgM+IgDlo B cell phenotype. Taken together, these results show that Plvap expression in endothelial cells is important in the maintenance of IgM+ B cells in the spleen and peritoneal cavity.

Safety and efficacy of the Gunther Tulip retrievable vena cava filter: midterm outcomes.

PURPOSE: To evaluate of the medium-term integrity, efficacy, and complication rate associated with the Gunther Tulip vena cava filter. METHODS: A retrospective study was performed of 369 consecutive patients who had infrarenal Gunther Tulip inferior vena cava filters placed over a 5-year period. The mean patient age was 61.8 years, and 59% were men. Venous thromboembolic disease and a contraindication to or complication of anticoagulation were the indications for filter placement in 86% of patients; 14% were placed for prophylaxis in patients with a mean of 2.3 risk factors. Follow-up was obtained by review of medical and radiologic records. RESULTS: Mean clinical follow-up was 780 days. New or recurrent pulmonary embolus occurred in 12 patients (3.3%). New or recurrent deep-vein thrombosis occurred in 53 patients (14.4%). There were no symptomatic fractures, migrations, or caval perforations. Imaging follow-up in 287 patients (77.8%) at a mean of 731 days revealed a single (0.3%) asymptomatic fracture, migration greater than 2 cm in 36 patients (12.5%), and no case of embolization. Of 122 patients with CT scans, asymptomatic perforations were identified in 53 patients (43.4%) at a mean 757 days. CONCLUSION: The Gunther Tulip filter was safe and effective at 2-year follow-up. Complication rates were similar to those reported for permanent inferior vena cava filters.

Caveolae, fenestrae and transendothelial channels retain PV1 on the surface of endothelial cells.

PV1 protein is an essential component of stomatal and fenestral diaphragms, which are formed at the plasma membrane of endothelial cells (ECs), on structures such as caveolae, fenestrae and transendothelial channels. Knockout of PV1 in mice results in in utero and perinatal mortality. To be able to interpret the complex PV1 knockout phenotype, it is critical to determine whether the formation of diaphragms is the only cellular role of PV1. We addressed this question by measuring the effect of complete and partial removal of structures capable of forming diaphragms on PV1 protein level. Removal of caveolae in mice by knocking out caveolin-1 or cavin-1 resulted in a dramatic reduction of PV1 protein level in lungs but not kidneys. The magnitude of PV1 reduction correlated with the abundance of structures capable of forming diaphragms in the microvasculature of these organs. The absence of caveolae in the lung ECs did not affect the transcription or translation of PV1, but it caused a sharp increase in PV1 protein internalization rate via a clathrin- and dynamin-independent pathway followed by degradation in lysosomes. Thus, PV1 is retained on the cell surface of ECs by structures capable of forming diaphragms, but undergoes rapid internalization and degradation in the absence of these structures, suggesting that formation of diaphragms is the only role of PV1.

The diaphragms of fenestrated endothelia: gatekeepers of vascular permeability and blood composition.

Fenestral and stomatal diaphragms are endothelial subcellular structures of unknown function that form on organelles implicated in vascular permeability: fenestrae, transendothelial channels, and caveolae. PV1 protein is required for diaphragm formation in vitro. Here, we report that deletion of the PV1-encoding Plvap gene in mice results in the absence of diaphragms and decreased survival. Loss of diaphragms did not affect the fenestrae and transendothelial channels formation but disrupted the barrier function of fenestrated capillaries, causing a major leak of plasma proteins. This disruption results in early death of animals due to severe noninflammatory protein-losing enteropathy. Deletion of PV1 in endothelium, but not in the hematopoietic compartment, recapitulates the phenotype of global PV1 deletion, whereas endothelial reconstitution of PV1 rescues the phenotype. Taken together, these data provide genetic evidence for the critical role of the diaphragms in fenestrated capillaries in the maintenance of blood composition.