Owen Caroline A
Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, 905 Thorn Building, 75 Francis Street, Boston, MA 02115, United States.
Int J Biochem Cell Biol. 2008;40(6-7):1246-72. doi: 10.1016/j.biocel.2008.01.020. Epub 2008 Jan 31.
A number of proteinases are expressed on the surface of leukocytes including members of the serine, metallo-, and cysteine proteinase superfamilies. Some proteinases are anchored to the plasma membrane of leukocytes by a transmembrane domain or a glycosyl phosphatidyl inositol (GPI) anchor. Other proteinases bind with high affinity to classical receptors, or with lower affinity to integrins, proteoglycans, or other leukocyte surface molecules. Leukocyte surface levels of proteinases are regulated by: (1) cytokines, chemokines, bacterial products, and growth factors which stimulate synthesis and/or release of proteinases by cells; (2) the availability of surface binding sites for proteinases; and/or (3) internalization or shedding of surface-bound proteinases. The binding of proteinases to leukocyte surfaces serves many functions including: (1) concentrating the activity of proteinases to the immediate pericellular environment; (2) facilitating pro-enzyme activation; (3) increasing proteinase stability and retention in the extracellular space; (4) regulating leukocyte function by proteinases signaling through cell surface binding sites or other surface proteins; and (5) protecting proteinases from inhibition by extracellular proteinase inhibitors. There is strong evidence that membrane-associated proteinases on leukocytes play critical roles in wound healing, inflammation, extracellular matrix remodeling, fibrinolysis, and coagulation. This review will outline the biology of membrane-associated proteinases expressed by leukocytes and their roles in physiologic and pathologic processes.
多种蛋白酶表达于白细胞表面，包括丝氨酸、金属和半胱氨酸蛋白酶超家族的成员。一些蛋白酶通过跨膜结构域或糖基磷脂酰肌醇（GPI）锚定在白细胞的质膜上。其他蛋白酶则以高亲和力与经典受体结合，或以较低亲和力与整合素、蛋白聚糖或其他白细胞表面分子结合。白细胞表面蛋白酶的水平受以下因素调节：（1）细胞因子、趋化因子、细菌产物和生长因子，它们刺激细胞合成和/或释放蛋白酶；（2）蛋白酶表面结合位点的可用性；和/或（3）表面结合蛋白酶的内化或脱落。蛋白酶与白细胞表面的结合具有多种功能，包括：（1）将蛋白酶的活性集中于紧邻细胞周围的环境；（2）促进酶原激活；（3）增加蛋白酶在细胞外空间的稳定性和保留；（4）通过蛋白酶通过细胞表面结合位点或其他表面蛋白发出信号来调节白细胞功能；（5）保护蛋白酶免受细胞外蛋白酶抑制剂的抑制。有强有力的证据表明，白细胞上的膜相关蛋白酶在伤口愈合、炎症、细胞外基质重塑、纤维蛋白溶解和凝血中起关键作用。本综述将概述白细胞表达的膜相关蛋白酶的生物学特性及其在生理和病理过程中的作用。
