Abstract
Cellular interaction is inevitable in the pathomechanism of human disease. Formation of heterotypic cellular aggregates, between distinct cells of hematopoietic and nonhematopoietic origin, may be involved in events leading to inflammation and the complex process of cancer progression. Among adhesion receptors, the family of selectins with their ligands have been considered as one of the major contributors to cell-cell interactions. Consequently, the inhibition of the interplay between selectins and their ligands may have potential therapeutic benefits. In this review, we focus on the current evidence on the selectins as crucial modulators of inflammatory, thrombotic, and malignant disorders. Knowing that there is promiscuity in selectin binding, we outline the importance of a key protein that serves as a ligand for all selectins. This dimeric mucin, the P-selectin glycoprotein ligand 1 (PSGL-1), has emerged as a major player in inflammation, thrombus, and cancer development. We discuss the interaction of PSGL-1 with various selectins in physiological and pathological processes with particular emphasis on mechanisms that lead to severe disease.
Highlights
In the last three decades, our knowledge on the function of the receptor family of selectins and their ligands has been substantially extended in terms of the development and progression of several diseases, inflammation, atherosclerosis, thrombosis, and malignancy
Several mucins expressed on cancer cells and neutrophil extracellular traps (NETs) have been recently implicated to be involved in thrombosis and cancer development via selectinmediated interaction
The Players and Their Nomenclature. Selectins obtained their names because of their ability to selectively bind carbohydrate moieties. Their ligands had long remained unidentified; work in the 1980s led to the discovery of a dimeric mucin that is uniformly designated as Pselectin glycoprotein ligand 1 (PSGL-1)
Summary
In the last three decades, our knowledge on the function of the receptor family of selectins and their ligands has been substantially extended in terms of the development and progression of several diseases, inflammation, atherosclerosis, thrombosis, and malignancy. It was found that nonactivated platelets do not react with S12, but following platelet activation by thrombin an intense labelling was obtained [3] Studies revealed that this clone identifies a 140 kDa protein that is present in the alpha-granules of resting platelets and upon stimulation is expressed on the cell surface [4]. A major breakthrough was the discovery that, to platelets, endothelial cells contain a considerable amount of P-selectin. After its synthesis, this protein is transported to the Golgi apparatus where it is decorated with carbohydrates and transported to and stored in the Weibel-Palade bodies [7].
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