Wagner D D
Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA.
Ciba Found Symp. 1995;189:2-10; discussion 10-16, 77-8. doi: 10.1002/9780470514719.ch2.
P-selectin is a transmembrane adhesion receptor specific to platelets and endothelial cells. It has an N-terminal lectin domain that recognizes specific carbohydrate moieties on monocytes, neutrophils and some other subsets of leukocytes. P-selectin is stored in granules and is expressed on the plasma membrane only after the cells are stimulated by vascular injury or during inflammation. Physiologically P-selectin is likely to be involved in the recruitment of leukocytes that promote wound healing and fight infection. There are many disorders in which the excessive recruitment of leukocytes is characteristic, including chronic inflammation, atherosclerosis, arthritis, diabetes, asthma and reperfusion injury. Because certain cancer cells also express the ligand for P-selectin it is possible that this receptor is involved in metastasis. To study the specific role of P-selectin in these pathological processes, we have prepared a mouse lacking P-selectin through gene targeting. Leukocyte interaction with the vessel wall is defective in these animals as leukocytes do not roll in the mesenteric venules and their extravasation at sites of inflammation and vessel injury is limited. We are testing these animals in models of the various diseases mentioned above in order to evaluate when the absence of P-selectin is beneficial.
P-选择素是一种血小板和内皮细胞特有的跨膜黏附受体。它有一个N端凝集素结构域，可识别单核细胞、中性粒细胞和其他一些白细胞亚群上的特定碳水化合物部分。P-选择素储存于颗粒中，只有在细胞受到血管损伤刺激或处于炎症状态时才会在质膜上表达。生理情况下，P-选择素可能参与促进伤口愈合和抵抗感染的白细胞募集过程。有许多病症的特征是白细胞过度募集，包括慢性炎症、动脉粥样硬化、关节炎、糖尿病、哮喘和再灌注损伤。由于某些癌细胞也表达P-选择素的配体，因此该受体可能参与转移过程。为了研究P-选择素在这些病理过程中的具体作用，我们通过基因靶向制备了缺乏P-选择素的小鼠。在这些动物中，白细胞与血管壁的相互作用存在缺陷，因为白细胞不会在肠系膜小静脉中滚动，并且它们在炎症和血管损伤部位的外渗受到限制。我们正在上述各种疾病模型中对这些动物进行测试，以评估缺乏P-选择素何时有益。
