Vascular adhesion protein-1, intercellular adhesion molecule-1 and P-Selectin mediate leukocyte binding to ischemic heart in humans

Jaakkola, Kimmo; Jalkanen, Sirpa; Kaunismäki, Katja; Vänttinen, E; Saukko, Pekka; Alanen, Kalle; Kallajoki, Markku; Voipio‐Pulkki, Liisa‐Maria; Salmi, Marko

doi:10.1016/s0735-1097(00)00706-3

Cited by 73 publications

(48 citation statements)

References 27 publications

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“…7 Here we have, for the first time, been able to analyze the role of SSAO activity in vivo. Our results indicate that VAP-1 and its enzymatic activity are important for PMN recruitment to the inflamed air pouch in rats.…”

Section: Discussionmentioning

confidence: 99%

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Granulocyte transmigration through the endothelium is regulated by the oxidase activity of vascular adhesion protein-1 (VAP-1)

Koskinen

Vainio²,

Smith³

et al. 2004

Blood

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116

148

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IntroductionWhite blood cells of the polymorphonuclear series (polymorphonuclear leukocytes [PMNs] or granulocytes) are practically absent from healthy tissues. Upon inflammation, however, rapid influx of PMNs from the blood into the affected tissue takes place. PMNs leave the blood mainly via postcapillary venules and they do not recirculate to any significant extent. Lymphocytes, on the other hand, not only exit at the sites of inflammation but also continuously recirculate between the blood and lymphoid tissues. The physiologic recirculation of lymphocytes is supported by specialized high endothelial venules in lymphoid tissues, and this leukocyte type returns back to the blood via the lymphatic vasculature. Monocytes, the third major leukocyte type, normally leave the blood at low levels in various tissues under normal conditions to replenish the tissue macrophage pools, and at high levels during the later phase of inflammation. The extravasation process of all leukocyte classes consists of a series of carefully controlled steps. [1][2][3] First, the leukocyte makes initial tethers with the luminal surface of the blood vessel and starts to roll along the endothelial lining. If it receives appropriate activation signals, it can adhere in a shear-resistant manner to the endothelium. Finally, the leukocyte transmigrates through the vascular wall and continues its odyssey toward the chemotactic inflammation-induced signals within the tissue. Multiple adhesion and signaling molecules act in concert to execute the emigration cascade. One of the endothelial molecules involved in lymphocyte trafficking is vascular adhesion protein-1 (VAP-1). 4 VAP-1 is a cell-surface enzyme belonging to a specific group of amine oxidases (semicarbazide-sensitive amine oxidases [SSAOs] Enzyme Commission 1.4.3.6) that catalyze oxidative deamination of primary amines. 5,6 Here we questioned what the possible mechanistic connection is between the adhesive and enzymatic activity of VAP-1. By using adenoviral constructs encoding native or mutated VAP-1, chemical inhibitors of SSAO activity, and function-blocking anti-VAP-1 monoclonal antibodies (mAbs) in in vitro flow chamber assays we were able to study the role of VAP-1 during PMN rolling, firm adhesion, and transmigration. Interestingly, VAP-1 primarily supported the transmigration step during the PMN extravasation process. Experiments with the SSAO inhibitors and VAP-1 mutants showed that the enzymatic activity of VAP-1 is a prerequisite for the adhesive function of this molecule. Finally, we showed in a rat model of acute inflammation that the new, specific, and potent SSAO inhibitor also blocks the recruitment of PMNs to affected tissue in vivo. These data show that VAP-1 functions in leukocyte adhesion in a step-wise fashion via separate antibody epitope-dependent and oxidation-dependent steps. These experiments are the first to show that an oxidative enzymatic reaction on the luminal surface of endothelial cells regulates PMN emigration in vitro and in vivo. Patients, materials, ...

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Section: Discussionmentioning

confidence: 99%

“…7 The cells were kept in Hanks Supported by the Finnish Academy, the Sigrid Juselius Foundation, the Technology Development Centre of Finland, the Finnish Cultural Foundation, and the European Union (QLG1-CT-1999-00295).…”

Section: Cells Dna Constructs and Adenoviral Transfectionsmentioning

confidence: 99%

Granulocyte transmigration through the endothelium is regulated by the oxidase activity of vascular adhesion protein-1 (VAP-1)

Koskinen

Vainio²,

Smith³

et al. 2004

Blood

Self Cite

116

148

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“…This may lead to endothelial activation and induction of VAP-1. 41 VAP-1 may then be involved in enhanced recruitment of monocytes [42][43][44][45] and Th1 CD4 cells 46 into the vessel wall. VAP-1-generated hydrogen peroxide also induces expression of classical endothelial adhesion molecules (P-selectin, MAdCAM-1), chemokines (CXCL8), and inflammatory transcription factors (nuclear factor-B, p53), 9 -11,47 and at high concentrations can be directly cytotoxic.…”

Section: Discussionmentioning

confidence: 99%

Soluble Vascular Adhesion Protein-1 Correlates With Cardiovascular Risk Factors and Early Atherosclerotic Manifestations

Aalto

Maksimow

Juonala

et al. 2012

ATVB

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Objective-Vascular adhesion protein-1 is an endothelial enzyme that regulates leukocyte traffic and contributes to vascular damage in animal models. The relations of soluble vascular adhesion protein-1 (sVAP-1) with cardiovascular risk factors and markers of subclinical atherosclerosis at a population level have not been studied. Key Words: adhesion molecules Ⅲ atherosclerosis Ⅲ epidemiology Ⅲ risk factors M igration of leukocytes from the blood into the vascular wall is important for the pathogenesis of atherosclerosis. 1,2 Adhesion molecules on the endothelial surface guide immigration of blood-borne leukocytes to various tissues, including vascular wall. Expression of many of these endothelial adhesion molecules is induced in inflammation. Most endothelial adhesion molecules are also found in plasma as soluble forms. 3 They are normally formed by shedding of the surface-bound molecules or by expression of alternatively spliced variants. Therefore, considerable interest has risen in the possibility of using soluble adhesion molecules as biomarkers for various inflammatory diseases, including atherosclerosis. 4 Vascular adhesion protein-1 (VAP-1) is an endothelial adhesion molecule involved in leukocyte migration from the blood into sites of inflammation. 5 In contrast to many other adhesion molecules, it is a cell-surface expressed enzyme. It belongs to semicarbazide-sensitive amine oxidases (also known as primary amine oxidases) that harbor oxidase activity in their extracellular domains. 6 VAP-1 oxidatively deaminates primary amines into aldehydes in a reaction that also produces hydrogen peroxide and ammonium. The enzymatic activity of VAP-1 is important for its adhesive function, 7,8 and it also modulates the inflammatory microenvironment through regulation of transcription factors, chemokines, and other adhesion molecules. 9 -11 Nevertheless, the biological end-products of VAP-1 catalyzed reaction are potentially cytotoxic at higher concentrations, and they are implied in the development of different vasculopathies. For instance, the involvement of VAP-1 in the production of endogenous aldehydes, reactive oxygen species, and advanced glycation end products and in the regulation of arterial structure have been proposed to lead to vascular damage in cellular and animal models. [12][13][14][15] A soluble form of VAP-1 (sVAP-1) is normally present in plasma. 16 The level of sVAP-1 is increased in certain inflam- Analyses of animal models and specific diseases thus suggest that VAP-1 may be involved in cardiovascular damage, but this has never been addressed at a population level. Here we developed a new high-throughput method for determining sVAP-1 activity in serum samples and correlated it to different cardiovascular risk factors and markers of subclinical atherosclerosis in a thoroughly characterized cohort of 2183 young Finns. Methods Study Subjects and Serum SamplesThe study cohort was from the Cardiovascular Risk in Young Finns Study. 25 It includes 3596 persons recruited in 1980 who have been exte...

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“…The molecular weight of human VAP-1 is distinct in different organs and even in one organ under pathological conditions. 25 The changes are believed to be because of alterations in carbohydrate structures of the molecules that are essential for the adhesive function of VAP-1. 9 Indeed, in canine and porcine tissues the molecular weight close to that of human VAP-1 and the expression pattern of the antigen detected in immunohistochemistry in both species together suggest that the molecules recognized by mAb 1B2 in canine and porcine tissues really are the homologues of human VAP-1.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Detection of Vascular Adhesion Protein-1 in Experimental Inflammation

Jaakkola

Nikula

Holopainen

et al. 2000

The American Journal of Pathology

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Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible endothelial glycoprotein which mediates leukocyte-endothelial cell interactions. To study the pathogenetic significance of VAP-1 in inflammatory disorders, an in vivo immunodetection method was used to detect the regulation of luminally expressed VAP-1 in experimental skin and joint inflammation in the pig and dog. Moreover, VAP-1 was studied as a potential target to localize inflammation by radioimmunoscintigraphy. Up-regulation of VAP-1 in experimental dermatitis and arthritis could be visualized by specifically targeted immunoscintigraphy. Moreover, the translocation of VAP-1 to the functional position on the endothelial surface was only seen in inflamed tissues. These results suggest that VAP-1 is both an optimal candidate for anti-adhesive therapy and a potential target molecule for imaging inflammation. Leukocyte migration into tissues is vital for efficient defense against insulting pathogens and foreign antigens. Nevertheless, the same phenomenon is also crucial to inappropriate inflammation and tissue destruction in several types of acute and chronic inflammatory and autoimmune diseases such as rheumatoid arthritis, inflammatory bowel diseases, organ transplant rejection, and ischemia-reperfusion injury. Leukocytes enter from the blood circulation into the tissues by passing through the walls of blood vessels. An essential step in this process is binding of leukocytes to the innermost layer of the blood vessel wall, the endothelium, by adhesion molecules. Multiple adhesion molecules on the leukocytes interact concertedly with their counter-receptors on the endothelium during the adhesion and the subsequent transmigration process.1,2 A change in the functional expression of adhesion molecules on the endothelial surface is an early and specific indicator of inflammation. In fact, recent studies suggest that radioactively labeled monoclonal antibodies against specific endothelial adhesion molecules can be used in the diagnosis of inflammation by nuclear imaging methods. 3,4Human vascular adhesion protein-1 (VAP-1), originally defined by 1B2 monoclonal antibody, is a 170-kd endothelial sialoglycoprotein.5 VAP-1 is inflammation inducible and mediates the early phases of interaction between lymphocytes and endothelium. 6 The expression pattern of VAP-1 in normal and inflamed human tissues has been described 7,8 and the role of VAP-1 in human leukocyte adhesion has been shown in vitro. 5,9 However, practically nothing is known about the translocation of VAP-1 from the inside of the cells to the functional position on the cell surface as well as the significance of VAP-1 in leukocyteendothelium interactions in vivo.The anti-human-VAP-1 mAb 1B2 does not recognize VAP-1 of small laboratory animals such as mouse, rat, or rabbit. However, preliminary screening experiments revealed that 1B2 antibody does recognize porcine and canine blood vessels. That encouraged us to study whether the antigens recognized by 1B2 are the porcine and canine homologues o...

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Vascular adhesion protein-1, intercellular adhesion molecule-1 and P-Selectin mediate leukocyte binding to ischemic heart in humans

Abstract: Human P-selectin, ICAM-1 and VAP-1 appear to be the most promising targets when antiadhesive interventions preventing leukocyte-mediated tissue destruction after myocardial ischemia are planned.

Cited by 73 publications

References 27 publications

Granulocyte transmigration through the endothelium is regulated by the oxidase activity of vascular adhesion protein-1 (VAP-1)

Granulocyte transmigration through the endothelium is regulated by the oxidase activity of vascular adhesion protein-1 (VAP-1)

Soluble Vascular Adhesion Protein-1 Correlates With Cardiovascular Risk Factors and Early Atherosclerotic Manifestations

In Vivo Detection of Vascular Adhesion Protein-1 in Experimental Inflammation

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