Fields Ryan C, Schoenecker Jonathan G, Hart Justin P, Hoffman Maureane R, Pizzo Salvatore V, Lawson Jeffrey H
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Am J Pathol. 2003 Jun;162(6):1817-22. doi: 10.1016/S0002-9440(10)64316-7.
Dendritic cells (DC) are potent antigen-presenting cells that govern the effector cell responses of the immune system. DC are thought to continuously develop from circulating progenitors in a process that is accelerated by inflammatory stimuli. However, the physiological signals that regulate the development of DC from precursor cells have not been well defined. Here we show that a serine protease acting via protease-activated receptor-2 (PAR-2) stimulates the development of DC from bone marrow progenitor cells cultured in granulocyte-macrophage colony-stimulating factor and IL-4. DC fail to develop in bone marrow cultures treated with soy bean trypsin inhibitor, a serine protease inhibitor, but this inhibition is overcome by a PAR-2 agonist peptide. DC do not spontaneously develop from the bone marrow of PAR-2-deficient mice, but can be stimulated to do so by inflammatory mediators. These results suggest that endogenous serine proteases stimulate DC development in vitro. Thus, serine proteases may help trigger adaptive immune responses in vivo.
树突状细胞（DC）是强大的抗原呈递细胞，可调控免疫系统的效应细胞反应。人们认为DC在炎症刺激加速的过程中持续从循环祖细胞发育而来。然而，调节DC从前体细胞发育的生理信号尚未明确界定。在此，我们表明，一种通过蛋白酶激活受体-2（PAR-2）起作用的丝氨酸蛋白酶可刺激在粒细胞-巨噬细胞集落刺激因子和白细胞介素-4中培养的骨髓祖细胞发育成DC。在用丝氨酸蛋白酶抑制剂大豆胰蛋白酶抑制剂处理的骨髓培养物中，DC无法发育，但PAR-2激动剂肽可克服这种抑制作用。DC不会从PAR-2缺陷小鼠的骨髓中自发发育，但可被炎症介质刺激发育。这些结果表明内源性丝氨酸蛋白酶在体外刺激DC发育。因此，丝氨酸蛋白酶可能有助于在体内触发适应性免疫反应。
