Liu W J, Hansen P J
Department of Dairy and Poultry Sciences, University of Florida, Gainesville 32611.
Endocrinology. 1995 Feb;136(2):779-87. doi: 10.1210/endo.136.2.7835310.
Dipeptidyl peptidase-IV (DPPIV) is a serine proteinase widely distributed in mammalian tissues, including lymphocytes, where it is identical to the T-cell activation antigen, cluster differentiation antigen-26. In the present study, DPPIV enzymatic activity was found in uterine secretions of unilaterally pregnant ewes in increasing amounts as gestation progressed. Progesterone increased DPPIV in uterine secretions from ovariectomized ewes and cows. DPPIV was enriched from ovine uterine secretions by a combination of cation exchange, gel filtration, lectin, and Gly-Pro-NH2 affinity chromatographies. The mol wt was 107 kilodaltons, as indicated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions, and 140 kilodaltons by gel filtration. The pI was estimated to be 6.8. Enzymatic activity had a pH optimum of 8.3 and a Km of 0.32 mM. The sequence of the 34 N-terminal amino acids was 77-87% homologous to an internal region of human cluster differentiation antigen-26 and rat liver DPPIV. Thus, uterine DPPIV appears to be missing the signal sequence that allows integration into the cytoplasmic membrane. DPPIV was localized immunohistochemically to lumenal and glandular endometrial epithelial cells and, in some pregnant ewes, discrete endometrial stromal cells. Highly enriched sheep uterine DPPIV costimulated proliferation of mitogen-treated sheep lymphocytes. Stimulation occurred in the presence of the uterine milk proteins, a pair of progesterone-induced endometrial secretory proteins with well characterized lymphocyte inhibitory activity. However, uterine milk proteins did not inhibit the costimulatory effect of DPPIV on phytohemagglutinin-L stimulated-lymphocyte proliferation. In conclusion, the uterine endometrium synthesizes a biologically active form of DPPIV under the influence of progesterone that is capable of enhancing mitogen-stimulated T-lymphocyte proliferation.
二肽基肽酶-IV（DPPIV）是一种丝氨酸蛋白酶，广泛分布于哺乳动物组织中，包括淋巴细胞，在淋巴细胞中它与T细胞活化抗原、簇分化抗原-26相同。在本研究中，发现单侧妊娠母羊的子宫分泌物中DPPIV酶活性随着妊娠进展而增加。孕酮可增加去卵巢母羊和母牛子宫分泌物中的DPPIV。通过阳离子交换、凝胶过滤、凝集素和甘氨酰-脯氨酰-氨基亲和层析相结合的方法，从绵羊子宫分泌物中富集了DPPIV。在还原条件下，十二烷基硫酸钠-聚丙烯酰胺凝胶电泳显示其分子量为107千道尔顿，凝胶过滤显示为140千道尔顿。估计其pI为6.8。酶活性的最适pH为8.3，Km为0.32 mM。34个N端氨基酸序列与人类簇分化抗原-26和大鼠肝脏DPPIV的内部区域有77%-87%的同源性。因此，子宫DPPIV似乎缺少允许整合到细胞质膜中的信号序列。免疫组织化学定位显示，DPPIV存在于子宫内膜腔面和腺上皮细胞中，在一些妊娠母羊中，也存在于离散的子宫内膜基质细胞中。高度富集的绵羊子宫DPPIV可共刺激经丝裂原处理的绵羊淋巴细胞增殖。这种刺激发生在子宫乳蛋白存在的情况下，子宫乳蛋白是一对由孕酮诱导的子宫内膜分泌蛋白，具有明确的淋巴细胞抑制活性。然而，子宫乳蛋白并不抑制DPPIV对植物血凝素-L刺激的淋巴细胞增殖的共刺激作用。总之，子宫内膜在孕酮的影响下合成一种具有生物活性的DPPIV形式，它能够增强丝裂原刺激的T淋巴细胞增殖。
