Ectoenzymes in leukocyte migration and their therapeutic potential

Abstract

Inflammation causes or accompanies a huge variety of diseases. Migration of leukocytes from the blood into the tissues, in the tissues, and from the tissues to lymphatic vasculature is crucial in the formation and resolution of inflammatory infiltrates. In addition to classical adhesion and activation molecules, several other molecules are known to contribute to the leukocyte traffic. Several of them belong to ectoenzymes, which are cell surface molecules having catalytically active sites outside the cell. We will review here how several ectoenzymes present on leukocytes or endothelial cell surface function as adhesins and/or modulate the extravasation cascade through their enzymatic activities. Moreover, their therapeutic potential as immune modulators in different experimental inflammation models and in clinical trials will be discussed.

Multivalent Interactions of Human Primary Amine Oxidase with the V and C22 Domains of Sialic Acid-Binding Immunoglobulin-Like Lectin-9 Regulate Its Binding and Amine Oxidase Activity

“…Additionally, sialic acids of the hAOC3-attached glycans are crucial for adhesion [13] and the hAOC3 glycosylation is important in the initial recognition but also regulates the enzymatic activity [14]. Since the small molecular inhibitors of hAOC3 oxidase activity are shown to prevent the inflammatory function of hAOC3 in vivo , the hAOC3 inhibitors could be used in treating acute and chronic inflammatory conditions as well as tumor progression and metastatic spread of cancer (reviewed in [15]).…”

The Ongoing Controversy

“…The leukocyte transmigration process includes distinct steps: (1) cell rolling, (2) adhesion, and (3) emigration ( Figure 3 ). 27 This process is supposed to be a protective process in the body under normal conditions, but it can cause secondary tissue damage during fluid resuscitation following ischemia. During the process of reperfusion of the ischemic tissues, endothelial cells are activated, which produces an increase in reactive oxygen species and less nitric oxide.…”

Severity markers in acute pancreatitis

“…CD73 also circulates in a soluble form in the blood [1]. We studied whether levels of soluble form of CD73 and cytokines/chemokines predict the development of organ failure in acute pancreatitis [2,3].…”