Selectins and scavenger receptors

Selectins (E-, L-, and P-selectin) and scavenger receptors (such as CD36 and SR-A) represent distinct classes of cell surface receptors that are integral to immune cell trafficking and metabolic homeostasis. Selectins are type-I transmembrane glycoproteins that mediate the initial tethering and rolling of leukocytes on the vascular endothelium, a critical step for immune cell recruitment to sites of inflammation [1][2]. Scavenger receptors are a structurally diverse group of proteins that recognize and internalize a wide range of ligands, including modified low-density lipoproteins (oxLDL), pathogens, and apoptotic cells, thereby bridging innate immunity and lipid metabolism [3][4]. These receptors are heavily implicated in the pathogenesis of atherosclerosis, chronic inflammatory disorders, and cancer metastasis, where they facilitate pathological cell-cell interactions or foam cell formation [1][3]. Therapeutic interventions include monoclonal antibodies like crizanlizumab, which targets P-selectin to prevent vaso-occlusive crises in sickle cell disease, and uproleselan, an E-selectin antagonist currently being evaluated for its ability to disrupt leukemic cell adhesion in the bone marrow [5][6]. While targeting these receptors offers significant therapeutic potential, challenges include maintaining adequate host defense mechanisms and avoiding off-target effects related to systemic lipid metabolism or tissue repair [1][3]. Sources: [1] Ley K. (2003). "The role of selectins in inflammation and disease." Trends in Molecular Medicine. [2] McEver R.P. (2015). "Selectins: lectins that initiate cell adhesion under flow." Current Opinion in Cell Biology. [3] Zani I.A., et al. (2015). "Scavenger Receptors: Role in Cell Biology and Pathology." Nutrients. [4] PrabhuDas M., et al. (2017). "Standardizing Scavenger Receptor Nomenclature." Journal of Immunology. [5] Ataga K.I., et al. (2017). "Crizanlizumab for the Prevention of Vaso-Occlusive Crises in Sickle Cell Disease." NEJM. [6] DeAngelo D.J., et al. (2022). "Uproleselan (GMI-1271) in combination with chemotherapy in AML." Blood.

Other names

Selectins and other immune cell surface/scavenger receptorsCell adhesion moleculesCD62 familyScavenger receptor familySRsLectin-like receptors

Selectin inhibitors block the interaction between selectins and their carbohydrate ligands (e.g., Sialyl-Lewis X) to prevent leukocyte adhesion and extravasation. Scavenger receptor modulators inhibit the binding and internalization of modified lipoproteins or pathogens to reduce foam cell formation and inflammatory signaling.