VAP-1 and CD73, Endothelial Cell Surface Enzymes in Leukocyte Extravasation

Jalkanen, Sirpa; Salmi, Marko

doi:10.1161/atvbaha.107.153130

Cited by 112 publications

(110 citation statements)

References 87 publications

(127 reference statements)

Supporting

Mentioning

105

Contrasting

Unclassified

Order By: Relevance

“…1 Here, we show VAP-1 expression in the resting and angiogenic corneal blood vessel endothelium. In the resting blood endothelium, VAP-1 is in intracellular vesicles, whereas in inflammation the molecule translocates onto the luminal surface in vivo.…”

Section: Discussionmentioning

confidence: 55%

“…14 VAP-1 regulates lymphocyte infiltration 1 and might thus indirectly regulate macrophage polarization. Aside from IL-4, other factors might also contribute to macrophage polarization in inflammatory angiogenesis.…”

Section: Vap-1 In Lymph-and Angiogenesis 1919mentioning

confidence: 99%

“…VAP-1 is expressed in pericytes and vascular endothelium and is involved in leukocyte extravasation to inflamed tissues. 1 Recently, we reported the expression of VAP-1 in the human eye 2 and the critical role it plays in ocular inflammatory diseases, such as uveitis, 3 age-related macular degeneration, 4 and diabetic retinopathy. 5 IL-1␤, a multipotent cytokine, is critically involved in the acute inflammatory response, activation and chemotaxis of inflammatory and antigen-presenting cells, up-regulation of adhesion molecules, and neovascularization.…”

mentioning

confidence: 99%

See 2 more Smart Citations

VAP-1–Mediated M2 Macrophage Infiltration Underlies IL-1β– but Not VEGF-A–Induced Lymph- and Angiogenesis

Nakao

Noda

Zandi

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

Vascular adhesion protein-1 (VAP-1) contributes to inflammatory and angiogenic diseases, including cancer and age-related macular degeneration. It is expressed in blood vessels and contributes to inflammatory leukocyte recruitment. The cytokines IL-1␤ and vascular endothelial growth factor A (VEGF-A) modulate angiogenesis, lymphangiogenesis, and leukocyte infiltration. The lymphatic endothelium expresses intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, which facilitate leukocyte transmigration into the lymphatic vessels. However, whether lymphatics express VAP-1 and whether they contribute to cytokine-dependent lymph-and angiogenesis are unknown. We investigated the role of VAP-1 in IL-1␤-and VEGF-A-induced lymph-and angiogenesis using the established corneal micropocket assay. IL-1␤ increased VAP-1 expression in the inflamed cornea. Our in vivo molecular imaging revealed significantly higher VAP-1 expression in neovasculature than in the preexisting vessels. VAP-1 was expressed in blood but not lymphatic vessels in vivo. IL-1␤-induced M2 macrophage infiltration and lymphand angiogenesis were blocked by VAP-1 inhibition. In contrast, VEGF-A-induced lymph-and angiogenesis were unaffected by VAP-1 inhibition. Our results indicate a key role for VAP-1 in lymph-and angiogenesisrelated macrophage recruitment. VAP-1 might become a new target for treatment of inflammatory lymph-and angiogenic diseases, including cancer.

show abstract

Section: Discussionmentioning

confidence: 55%

Section: Vap-1 In Lymph-and Angiogenesis 1919mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

VAP-1–Mediated M2 Macrophage Infiltration Underlies IL-1β– but Not VEGF-A–Induced Lymph- and Angiogenesis

Nakao

Noda

Zandi

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…Both hydrogen peroxide and aldehydes are biologically potent molecules capable of causing tissue damage due to their cytotoxicity at high concentrations [16]. However, at low physiological concentrations, H 2 O 2 has signaling functions regulating leukocyte-endothelial interaction [17]. The adhesive function of VAP-1 mediates leukocyte rolling, firm adhesion and transmigration from the luminal surface of the endothelium to the tissue [17,18].…”

mentioning

confidence: 99%

“…Interestingly, other ectoenzymes, such as CD39 and CD73, have also recently been shown to be crucial for ALI development [25,31]. Thus, this diverse class of ectoenzymes can contribute to the IR injury to the same extent as the classical adhesion molecules, and should therefore be considered as potential therapeutic target for these disorders.VAP-1 has two functional modalities (enzyme-activitydependent and enzyme-activity-independent) [17]. In all previous inflammatory models directly comparing the two functions, both functions have contributed to the adhesive role of VAP-1.…”

mentioning

confidence: 99%

Ischemia‐reperfusion injury is attenuated in VAP‐1‐deficient mice and by VAP‐1 inhibitors

et al. 2008

Self Cite

View full text Add to dashboard Cite

Neutrophils mediate the damage caused by ischemia-reperfusion both at the site of primary injury and in remote organs. Vascular adhesion protein-1 (VAP-1) is an ectoenzyme expressed on endothelial cells and it has been shown to regulate leukocyte extravasation. Here we show for the first time using VAP-1-deficient mice that VAP-1 plays a significant role in the intestinal damage and acute lung injury after ischemiareperfusion. Separate inhibition of VAP-1 by small molecule enzyme inhibitors and a function-blocking monoclonal antibody in WT mice revealed that the catalytic activity of VAP-1 is responsible for its pro-inflammatory action. The use of transgenic humanized VAP-1 mice also showed that the enzyme inhibitors alleviate both the ischemia-reperfusion injury in the gut and neutrophil accumulation in the lungs. These data thus indicate that VAP-1 regulates the inflammatory response in ischemia-reperfusion injury and suggest that blockade of VAP-1 may have therapeutic value.Key words: Adhesion molecules . Inflammation . Ischemia-reperfusion injury IntroductionInteraction between leukocytes and endothelium, which allows leukocyte extravasation to the tissues, forms an essential part of host defense. This interaction is mediated via adhesion molecules expressed on the surface of leukocytes and endothelium [1]. Although indispensable for normal immune response, increased leukocyte trafficking to the tissues has deleterious consequences in certain diseases [2][3][4][5].Diseases caused by ischemia are the leading cause of death in the developed countries. Since ischemia causes tissue necrosis, its treatment consists of restoration of blood flow to the ischemic tissue. Although reperfusion is necessary to prevent further damage to the ischemic tissue, it triggers an inflammatory response that aggravates ischemia-induced tissue damage [6]. Therefore, ischemia-reperfusion (IR) injury (IRI) complicates treatment of many potentially fatal diseases. A hallmark of IRI is sequestration of neutrophils in the reperfused tissues. Excessive neutrophil extravasation is to a large extent a consequence of increased expression and/or avidity of adhesion molecules on the surface of endothelial cells and neutrophils [1,7].Inflammatory response to IR can cause damage not only in reperfused tissues but also in remote organs. Pro-inflammatory cytokines released at the site of reperfusion enter circulation and activate endothelium and circulating leukocytes in multiple vascular beds [2,6]. Although systemic inflammatory response may lead to development of dysfunction anywhere in the body, lungs are the most frequently injured organ [8,9]. Indirect acute lung injury (ALI) can appear alone or as a part of multiple organ dysfunction syndrome, in which it is a strong independent risk factor for death [10]. Since increased leukocyte trafficking plays a major role in both IR and remote organ injury, identification of the molecules involved in neutrophil infiltration is of paramount importance for the development of an effective treatment. Va...

show abstract

Inhibitors of Leukocyte Adhesion and Migration in Phase 1 and 2 Clinical Studies for Immunological Disorders

Brennan

2014

Handbook of Therapeutic Antibodies

View full text Add to dashboard Cite

VAP-1 and CD73, Endothelial Cell Surface Enzymes in Leukocyte Extravasation

Cited by 112 publications

References 87 publications

VAP-1–Mediated M2 Macrophage Infiltration Underlies IL-1β– but Not VEGF-A–Induced Lymph- and Angiogenesis

VAP-1–Mediated M2 Macrophage Infiltration Underlies IL-1β– but Not VEGF-A–Induced Lymph- and Angiogenesis

Ischemia‐reperfusion injury is attenuated in VAP‐1‐deficient mice and by VAP‐1 inhibitors

Inhibitors of Leukocyte Adhesion and Migration in Phase 1 and 2 Clinical Studies for Immunological Disorders

Contact Info

Product

Resources

About