Lack of endothelial diaphragms in fenestrae and caveolae of mutant Plvap-deficient mice

Herrnberger, Leonie; Seitz, R; Kuespert, Sabrina; Bösl, Michael R.; Fuchshofer, Rudolf; Tamm, Ernst R.

doi:10.1007/s00418-012-0987-3

Cited by 68 publications

(86 citation statements)

References 37 publications

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Section: Roles Of Plvap In Physiological Processesmentioning

confidence: 99%

“…On a C57BL/6N genetic background, PLVAP-null embryos died before birth and suffered from edema, hemorrhages, and defects to the vascular wall of subcutaneous capillaries (36). Furthermore, diaphragms were missing from caveolae of the subcutaneous capillaries and endocardium ECs of PLVAP-null mice (36). In addition, capillaries of the pancreas and kidney peritubular interstitium of PLVAP-null mice demonstrated a complete absence of diaphragms in fenestrae, caveolae, and TECs (36).…”

Section: Roles Of Plvap In Physiological Processesmentioning

confidence: 99%

“…Furthermore, diaphragms were missing from caveolae of the subcutaneous capillaries and endocardium ECs of PLVAP-null mice (36). In addition, capillaries of the pancreas and kidney peritubular interstitium of PLVAP-null mice demonstrated a complete absence of diaphragms in fenestrae, caveolae, and TECs (36). Transmission electron microscopy confirmed the lack of endothelial integrity, detecting extensive defects in the endothelial lining of capillaries (36).…”

Section: Roles Of Plvap In Physiological Processesmentioning

confidence: 99%

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Plasmalemma vesicle-associated protein: A crucial component of vascular homeostasis

Guo

Zhang

Hou

et al. 2016

Experimental and Therapeutic Medicine

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Endothelial subcellular structures, including caveolae, fenestrae and transendothelial channels, are crucial for regulating microvascular function. Plasmalemma vesicle-associated protein (PLVAP) is an endothelial cell-specific protein that forms the stomatal and fenestral diaphragms of blood vessels and regulates basal permeability, leukocyte migration and angiogenesis. Loss of PLVAP in mice leads to premature mortality due to disrupted homeostasis. Evidence from previous studies suggested that PLVAP is involved in cancer, traumatic spinal cord injury, acute ischemic brain disease, transplant glomerulopathy, Norrie disease and diabetic retinopathy. Specifically, PLVAP expression has been demonstrated to be upregulated in these diseases, accompanied by pro-angiogenic or pro-inflammatory responses. Therefore, PLVAP is considered a novel therapeutic target, in addition to an endothelial cell marker. The present review summarizes the structure and functions of PLVAP, and its roles in pathophysiological processes.

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Section: Roles Of Plvap In Physiological Processesmentioning

confidence: 99%

Section: Roles Of Plvap In Physiological Processesmentioning

confidence: 99%

Section: Roles Of Plvap In Physiological Processesmentioning

confidence: 99%

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Plasmalemma vesicle-associated protein: A crucial component of vascular homeostasis

Guo

Zhang

Hou

et al. 2016

Experimental and Therapeutic Medicine

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“…18,19 PV1 is a transmembrane glycoprotein that has been localized to caveolae and trans-endothelial channels of systemic fenestrated capillaries where it regulates vascular permeability. [20][21][22] Furthermore, it has been recently shown that PV1 is not only expressed on blood vessels but also on lymphatic endothelial cells where it forms a physical filter that modulates the passage of soluble antigens and the transmigration of lymphocytes. 23 Interestingly, we found that the expression of PV1 is up-regulated on blood capillaries upon infection with Salmonella typhimurium, an enteric pathogen known to disseminate systemically.…”

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confidence: 99%

Gene expression profile of endothelial cells during perturbation of the gut vascular barrier

et al. 2016

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It has been widely demonstrated that tolerance against gut microbiota is compartmentalized to mucosal sites where microbes mostly reside. How the commensal bacteria are excluded from the entrance into the blood stream via intestinal capillaries that are located beneath the gut epithelium was not clear. We recently described the existence of a new anatomical structure, the 'gut vascular barrier' (GVB), both in murine and human intestines that plays a fundamental role in avoiding indiscriminate trafficking of bacteria from the gut into the blood circulation. The vascular barrier integrity could be altered by Salmonella typhimurium, a pathogen capable of systemic dissemination, through the modulation of the Wnt/b-catenin signaling pathway. Here we have analyzed the differences in gut endothelial gene expression profiles during Salmonella infection and have identified some interesting characteristics of endothelial to mesenchymal transition. These findings add new insights in the gut-liver axis. The intestine is continuously exposed to a huge amount of foreign antigens, mostly food proteins and commensal microorganisms. These harmless antigens induce oral tolerance, which is however different when considering gut bacteria or food antigens. Tolerance to food proteins affects both local and systemic immune responses 1 indeed fed soluble antigens can gain access to the lymphatics to reach the mesenteric lymph nodes (mLN) 2 and the blood stream to reach the liver 3 where oral tolerance is established. By contrast, gut microbes are confined at mucosal sites by the mLNs that function like a firewall avoiding the spreading of intestinal microflora through the thoracic duct into the blood circulation. [4][5][6] Therefore at steady state the systemic immune system is left ignorant to the microbiota. Only during intestinal pathology bacteria can reach the liver that acts as a firewall preventing the bacteria from spreading to other systemic sites. 7 How the microbiota recirculates through the lymphatics has been widely studied, while how intestinal bacteria are excluded from the blood circulation was completely unexplored, even though it is known that intestinal capillaries are located just underneath the epithelial layer whereas the lymphatics are much deeper in the lamina propria.In our recent work, we hypothesized the existence of a barrier at the endothelial level, the 'gut vascular barrier' (GVB), 8 that similarly to the blood brain barrier (BBB) is able to control the type of antigens that can translocate into the blood stream and that is not permissive to bacterial penetration.Drawing a parallelism between the well-known BBB and the newly identified GVB many similarities can be found. Both are able to avoid the indiscriminate movement of molecules, cells and bacteria from blood to the brain parenchyma in the BBB and from the intestinal lumen into the blood circulation in the case of the GVB.

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“…Microscopic (19, 22) and genetic (26, 28, 29) lines of investigation led to the conclusion that Plvap is specifically expressed in the endothelial cells of blood vessel capillaries and venules in select vascular beds and in the heart endocardium and absent from lymphatic endothelial cells. This pattern of expression was fully supported by a large body of literature obtained with two endothelial specific monoclonal antibodies that bind Plvap, such as MECA-32 (30, 31) in the mouse and PAL-E (32–34) in humans (reviewed in (35, 36)).…”

Section: Introductionmentioning

confidence: 99%

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

Elgueta

Tse

Deharvengt

et al. 2016

The Journal of Immunology

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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 antigens 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 peritoneal cavity. Tissue specific deletion of Plvap demonstrates that the defect is B cell extrinsic, as 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.

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Lack of endothelial diaphragms in fenestrae and caveolae of mutant Plvap-deficient mice

Cited by 68 publications

References 37 publications

Plasmalemma vesicle-associated protein: A crucial component of vascular homeostasis

Plasmalemma vesicle-associated protein: A crucial component of vascular homeostasis

Gene expression profile of endothelial cells during perturbation of the gut vascular barrier

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

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