Role for protease cascade in humaral and cellular immunity of insects

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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