E-Selectin Ligands in the Human Mononuclear Phagocyte System: Implications for Infection, Inflammation, and Immunotherapy

Abstract

The mononuclear phagocyte system comprises a network of circulating monocytes and dendritic cells (DCs), and “histiocytes” (tissue-resident macrophages and DCs) that are derived in part from blood-borne monocytes and DCs. The capacity of circulating monocytes and DCs to function as the body’s first-line defense against offending pathogens greatly depends on their ability to egress the bloodstream and infiltrate inflammatory sites. Extravasation involves a sequence of coordinated molecular events and is initiated by E-selectin-mediated deceleration of the circulating leukocytes onto microvascular endothelial cells of the target tissue. E-selectin is inducibly expressed by cytokines (tumor necrosis factor-α and IL-1β) on inflamed endothelium, and binds to sialofucosylated glycan determinants displayed on protein and lipid scaffolds of blood cells. Efficient extravasation of circulating monocytes and DCs to inflamed tissues is crucial in facilitating an effective immune response, but also fuels the immunopathology of several inflammatory disorders. Thus, insights into the structural and functional properties of the E-selectin ligands expressed by different monocyte and DC populations is key to understanding the biology of protective immunity and the pathobiology of several acute and chronic inflammatory diseases. This review will address the role of E-selectin in recruitment of human circulating monocytes and DCs to sites of tissue injury/inflammation, the structural biology of the E-selectin ligands expressed by these cells, and the molecular effectors that shape E-selectin ligand cell-specific display. In addition, therapeutic approaches targeting E-selectin receptor/ligand interactions, which can be used to boost host defense or, conversely, to dampen pathological inflammatory conditions, will also be discussed.

Influence of Cardiometabolic Risk Factors on Platelet Function

“…As extensively reviewed [29][30][31], once adhered to the damaged vessel wall platelets participate in multiple mechanisms promoting thromboinflammation by releasing storage granules and aggregating to form thrombi. As mentioned, platelet adhesion is influenced by adhesion molecules present in the subendothelial matrix components, such as E-selectin [32], vWF [33], collagen, fibronectin, and by the level of shear stress in the circulation [34]. In this phase, platelets are subjected to a number of physiological and cytoskeletal changes, with release of soluble cytokines, chemokines, growth factors, and the rapid translocation of P-selectin from alpha-granule to plasma membrane.…”

Targeted transcriptional profiling of the tumor microenvironment reveals lymphocyte exclusion and vascular dysfunction in metastatic osteosarcoma

“…25,30,31 Due to the T cell exclusion observed in metastatic OS ( Figure 5), we focused our attention towards further investigating the relationship between vascular function and lymphocyte abundance. E-selectin, encoded by the SELE gene, is an endothelial cell adhesion molecule that facilitates leukocyte tethering and rolling on the vascular wall, the first step in [32][33][34] Whereas ICAM1 and PECAM1 can be expressed in both endothelial cells and tumor cells, SELE is expressed exclusively in endothelial cells and is transcriptionally upregulated in response to inflammation, thus serving as a marker of an activated and functional endothelium. [34][35][36][37][38][39][40] Our results demonstrate that the expression of SELE is significantly lower in the metastatic OS specimens (Figure 6a).…”

Modification of human MSC surface with oligopeptide‐PEG‐lipids for selective binding to activated endothelium

“…35 However, there are a number of target receptors expressed on the cell surface under ischemia: for examples, some cell adhesion molecules including VCAM-1, ICAM-1 are highly expressed. E-selectin is chosen as one of the target receptors expressed on activated endothelium.…”

“…E-selectin is chosen as one of the target receptors expressed on activated endothelium. 35 However, there are a number of target receptors expressed on the cell surface under ischemia: for examples, some cell adhesion molecules including VCAM-1, ICAM-1 are highly expressed. 36 Since the level and timing of the expression are different among those receptors during the ischemia, it is unclear that which receptors should be the responsible target for MSC delivery.…”