Ley Klaus
Cardiovascular Research Center, MR5 Building, Room 1013, University of Virginia, PO Box 801394, Charlottesville, VA 22908-1394, USA.
Trends Mol Med. 2003 Jun;9(6):263-8. doi: 10.1016/s1471-4914(03)00071-6.
Selectins are carbohydrate-binding molecules that bind to fucosylated and sialylated glycoprotein ligands, and are found on endothelial cells, leukocytes and platelets. They are involved in trafficking of cells of the innate immune system, T lymphocytes and platelets. An absence of selectins or selectin ligands has serious consequences in mice or humans, leading to recurrent bacterial infections and persistent disease. Selectins are involved in constitutive lymphocyte homing, and in chronic and acute inflammation processes, including post-ischemic inflammation in muscle, kidney and heart, skin inflammation, atherosclerosis, glomerulonephritis and lupus erythematosus. Selectin-neutralizing monoclonal antibodies, recombinant soluble P-selectin glycoprotein ligand 1 and small-molecule inhibitors of selectins have been tested in clinical trials on patients with multiple trauma, cardiac indications and pediatric asthma, respectively. Anti-selectin antibodies have also been successfully used in preclinical models to deliver imaging contrast agents and therapeutics to sites of inflammation. Further improvements in the efficiency, availability, specificity and pharmacokinetics of selectin inhibitors, and specialized application routes and schedules, hold promise for therapeutic indications.
选择素是一类能与岩藻糖基化和唾液酸化糖蛋白配体结合的碳水化合物结合分子，存在于内皮细胞、白细胞和血小板表面。它们参与固有免疫系统细胞、T淋巴细胞和血小板的运输。在小鼠或人类中，缺乏选择素或选择素配体会产生严重后果，导致反复细菌感染和持续性疾病。选择素参与组成性淋巴细胞归巢以及慢性和急性炎症过程，包括肌肉、肾脏和心脏的缺血后炎症、皮肤炎症、动脉粥样硬化、肾小球肾炎和红斑狼疮。选择素中和单克隆抗体、重组可溶性P选择素糖蛋白配体1以及选择素小分子抑制剂已分别在多创伤患者、心脏疾病患者和儿童哮喘患者的临床试验中进行了测试。抗选择素抗体也已在临床前模型中成功用于将成像造影剂和治疗药物递送至炎症部位。选择素抑制剂在效率、可用性、特异性和药代动力学方面的进一步改进以及专门的应用途径和方案，有望用于治疗相关病症。
