Role for protease cascade in humaral and cellular immunity of insects

生长阻断肽（Growth-blocking peptide，GBP）是一种由25个氨基酸组成的昆虫细胞因子，存在于鳞翅目昆虫中，具有调节幼虫生长、刺激免疫细胞等多种生物学活性。我们确定了鳞翅目GBP在其他昆虫目中的同源肽。从鞘翅目和双翅目昆虫幼虫中分离纯化了两种新的细胞因子。果蝇和冈比亚按蚊基因组数据库的同源性搜索的苍蝇细胞因子发现三个果蝇和两个蚊子的同源物，这表明广泛传播的发生这个细胞因子家族。此外，还从鳞翅目昆虫中分离到一种GBP-binding蛋白。对GBP与结合蛋白相互作用的动力学和生物学分析表明，GBP与结合蛋白的强结合通过刺激完全不同类型的细胞来调节细胞免疫反应，昆虫血淋巴中的酚氧化酶原级联反应在识别外源物和防御机制中起着重要作用。 ...更多信息 汉化。这种级联反应是由微生物细胞壁成分触发的，例如来自真菌的β-1，3-葡聚糖和来自细菌的肽聚糖，导致局部黑化。为了研究级联激活的机制，我们鉴定了家蚕proPO级联的三个新组分（βGRPII、GNBP、因子S）。βGRPII和GNBP分别参与β-1，3-葡聚糖和肽聚糖介导的级联途径。因子S是一种丝氨酸蛋白酶酶原，位于模式识别蛋白和proBAEEase之间，是黑色素合成的proPO激活途径和proBAEEase激活途径的重要组成部分。此外，BAEEase被证明可以将果蝇pro-spatzle加工成spatzle，这是Toll介导的途径上的一种类似于甜菜碱的配体，用于控制果蝇免疫中某些抗菌肽的合成。这些结果表明，proPO级联的昆虫是一种细胞外信号机制，识别PAMPs作为外源性的诱导急性期蛋白质的合成，而不仅仅是一个效应机制的黑色素的生产。少

Growth-blocking peptide (GBP) is a 25 amino acid insect cytokine found in Lepidopteran insects that possesses diverse biological activities such as larval growth regulation and stimulation of immune cells. We identified homologous peptides of the Lepidopteran GBP in the other orders of insects. Two novel cytokines were purified from coleopteran and dipteran larvae. Homology search of the Drosophila melanogaster and Anopheles gambiae genome database for the fly cytokine revealed three drosophila and two mosquito homologues, suggesting wide-spread occurrence of this cytokine family. Furthermore, a GBP-binding protein was isolated from Lepidopteran. Kinetic and biological analyses of interaction between GBP and the binding protein showed their strong binding regulates cellular immunoreaction through the stimulation of completely different types of the cells.The prophenoloxidase (proPO) cascade of insect hemolymph plays some important roles in the recognition of foreignness and defense mec … More hanism. The cascade is triggered by microbial cell wall components such as β-1,3-glucan from fungi and peptidoglycan from bacteria, resulting in localized melanization. To investigate the mechanism for the activation of the cascade, we identified three new components (βGRPII, GNBP, Factor S) of the silkworm proPO cascade. βGRPII and GNBP are involved in β-1,3-glucan-and peptidoglycan- mediated pathways of the cascade, respectively. Factor S is a serine protease zymogen, which is located between the pattern recognition proteins and proBAEEase and is an essential component both in the proPO-activating pathway for melanin synthesis and in proBAEEase-activating pathway. Moreover, BAEEase was shown to process Drosophila pro-spatzle to spatzle, which is a cytokine-like ligand on Toll-mediated pathway for control of the synthesis of some anti-microbial peptides in Drosophila immunity. These results suggests that the proPO cascade of insects is an extracellular signaling mechanism for recognizing PAMPs as foreignness in the induction of acute-phase protein synthesis, not only an effector mechanism for the production of melanin. Less