Foster C A
Department of General Dermatology, Sandoz Research Institute, Vienna, Austria.
J Allergy Clin Immunol. 1996 Dec;98(6 Pt 2):S270-7. doi: 10.1016/s0091-6749(96)70075-1.
Lymphocyte recirculation and leukocyte extravasation involve a multistep process that is central to immune surveillance and the rapid response of white blood cells to sites of injury or infection. Interaction of vascular adhesion molecules (VCAM-1, ICAM-1, and selectins) with ligands on the leukocyte surface (integrins, carbohydrates, and mucin-like molecules) regulate diapedesis. The nature of an inflammatory stimulus ultimately determines the pattern of endothelial adhesion molecule expression and the avidity state of their counterreceptors, thus dictating to a large extent whether a subclass of leukocytes will play a dominant role in the immune response. Immunoglobulin superfamily member VCAM-1 recognizes alpha 4 beta 1 integrin, expressed on all leukocytes except neutrophils. Blockade or inhibition of VCAM-1/alpha 4 beta 1 interaction is expected to have therapeutic potential in treating various inflammatory disorders and autoimmune diseases since this adhesion pathway has a major influence on eosinophil, lymphocyte, and monocyte trafficking. This review summarizes some of the strategies that are currently used to selectively inhibit the VCAM-1/alpha 4 integrin pathway, including soluble VCAM-Ig fusion protein, peptide antagonists, antisense oligonucleotides, natural products, and neutralizing antibodies to VCAM-1 or alpha 4 integrin.
淋巴细胞再循环和白细胞外渗涉及一个多步骤过程，这对于免疫监视以及白细胞对损伤或感染部位的快速反应至关重要。血管黏附分子（血管细胞黏附分子-1、细胞间黏附分子-1和选择素）与白细胞表面配体（整合素、碳水化合物和黏蛋白样分子）的相互作用调节白细胞渗出。炎症刺激的性质最终决定内皮黏附分子的表达模式及其反受体的亲和力状态，从而在很大程度上决定白细胞亚类是否会在免疫反应中起主导作用。免疫球蛋白超家族成员血管细胞黏附分子-1识别α4β1整合素，α4β1整合素在除中性粒细胞外的所有白细胞上表达。由于这种黏附途径对嗜酸性粒细胞、淋巴细胞和单核细胞的迁移有重大影响，因此阻断或抑制血管细胞黏附分子-1/α4β1相互作用有望在治疗各种炎症性疾病和自身免疫性疾病方面具有治疗潜力。本综述总结了目前用于选择性抑制血管细胞黏附分子-1/α4整合素途径的一些策略，包括可溶性血管细胞黏附分子-免疫球蛋白融合蛋白、肽拮抗剂、反义寡核苷酸、天然产物以及针对血管细胞黏附分子-1或α4整合素的中和抗体。
