Lah T T, Hawley M, Rock K L, Goldberg A L
Albert Einstein Medical Center, Department of Pathology and Laboratory of Medicine, Philadelphia, PA 19141, USA.
FEBS Lett. 1995 Apr 17;363(1-2):85-9. doi: 10.1016/0014-5793(95)00287-j.
Previous studies have indicated that acid-optimal cysteine proteinase(s) in the endosomal-lysosomal compartments, cathepsins, play a critical role in the proteolytic processing of endocytosed proteins to generate the antigenic peptides presented to the immune system on major histocompatibility complex (MHC) class II molecules. The presentation of these peptides and the expression of MHC class II molecules by macrophages and lymphocytes are stimulated by gamma-interferon (gamma-IFN). We found that treatment of human U-937 monocytes with gamma-IFN increased the activities and the content of the two major lysosomal cysteine proteinases, cathepsins B and L. Assays of protease activity, enzyme-linked immunosorbant assays (ELISA) and immunoblotting showed that this cytokine increased the amount of cathepsin B 5-fold and cathepsin L 3-fold in the lysosomal fraction. By contrast, the aspartic proteinase, cathepsin D, in this fraction was not significantly altered by gamma-IFN treatment. An induction of cathepsins B and L was also observed in mouse macrophages, but not in HeLa cells. These results suggest coordinate regulation in monocytes of the expression of cathepsins B and L and MHC class II molecules. Presumably, this induction of cysteine proteases contributes to the enhancement of antigen presentation by gamma-IFN.
先前的研究表明，内体-溶酶体区室中的酸性最佳半胱氨酸蛋白酶（组织蛋白酶）在对内吞蛋白质进行蛋白水解加工以产生在主要组织相容性复合体（MHC）II类分子上呈递给免疫系统的抗原肽过程中起关键作用。巨噬细胞和淋巴细胞对这些肽的呈递以及MHC II类分子的表达受到γ-干扰素（γ-IFN）的刺激。我们发现用γ-IFN处理人U-937单核细胞会增加两种主要溶酶体半胱氨酸蛋白酶组织蛋白酶B和L的活性及含量。蛋白酶活性测定、酶联免疫吸附测定（ELISA）和免疫印迹表明，这种细胞因子使溶酶体部分中的组织蛋白酶B含量增加了5倍，组织蛋白酶L增加了3倍。相比之下，该部分中的天冬氨酸蛋白酶组织蛋白酶D并未因γ-IFN处理而发生显著改变。在小鼠巨噬细胞中也观察到了组织蛋白酶B和L的诱导，但在HeLa细胞中未观察到。这些结果表明，单核细胞中组织蛋白酶B和L的表达与MHC II类分子的表达存在协同调节。据推测，这种对半胱氨酸蛋白酶的诱导有助于γ-IFN增强抗原呈递。
