No abstract

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...

Changes in endothelial permeability are crucial in the pathogenesis of many diseases. Adenosine is one of the endogenous mediators controlling endothelial permeability under normal conditions, and an endothelial cell surface enzyme CD73 is a key regulator of adenosine production. Here we report that IFN-b is a novel inducer of CD73. We found that pretreatment with IFN-b dramatically improved the vascular barrier function in lungs after intestinal ischemia-reperfusion injury in wild-type animals in vivo. IFN-b had absolutely no protective effects in CD73-deficient mice, which suffered from more severe lung damage than wild-type mice, showing that IFN-b functions strictly in a CD73-dependent manner. Most importantly, IFN-b treatment initiated after the ischemic period almost completely inhibited vascular leakage during the reperfusion. IFN-b also induced the expression and activity of CD73 and concurrently decreased vascular permeability in cultured human pulmonary endothelial cells. These data show that induction of CD73 and improvement of vascular barrier are new mechanisms for the anti-inflammatory action of IFN-b. Moreover, IFN-b treatment may be useful in alleviating vascular leakage induced by ischemia-reperfusion injury.

Background: Only a few previous studies have focused on the long-term prognosis of the patients with infective endocarditis (IE). Our purpose was to delineate factors potentially associated with the long-term outcome of IE, recurrences of IE and requirement for late valve surgery.