Bidla Gawa, Dushay Mitchell S, Theopold Ulrich
Department of Molecular Biology and Functional Genomics, University of Stockholm, Svante Arrheniusväg 16-18, SE 10691 Stockholm, Sweden.
J Cell Sci. 2007 Apr 1;120(Pt 7):1209-15. doi: 10.1242/jcs.03420. Epub 2007 Mar 13.
The prophenoloxidase-activating cascade is a key component of arthropod immunity. Drosophila prophenoloxidase is stored in crystal cells, a specialized class of blood cells from which it is released through cell rupture. Within minutes after bleeding, prophenoloxidase is activated leading to visible melanization of the clot matrix. Using crystal cell rupture and melanization as readouts to screen mutants in signal transduction pathways, we show that prophenoloxidase release requires Jun N-terminal kinase, small Rho GTPases and Eiger, the Drosophila homolog of tumor necrosis factor. We also provide evidence that in addition to microbial products, endogenous signals from dying hemocytes contribute to triggering and/or assembly of the prophenoloxidase-activating cascade, and that this process can be inhibited in vitro and in vivo using the viral apoptotic inhibitor p35. Our results provide a more comprehensive view of immune signal transduction pathways, with implications for immune reactions where cell death is used as a terminal mode of cell activation.
酚氧化酶原激活级联反应是节肢动物免疫的关键组成部分。果蝇酚氧化酶原储存在晶细胞中，晶细胞是一类特殊的血细胞，酚氧化酶原通过细胞破裂从中释放出来。出血后几分钟内，酚氧化酶原被激活，导致凝块基质出现可见的黑化现象。利用晶细胞破裂和黑化作为筛选信号转导途径突变体的指标，我们发现酚氧化酶原的释放需要Jun N端激酶、小Rho GTP酶和Eiger（肿瘤坏死因子的果蝇同源物）。我们还提供了证据表明，除了微生物产物外，来自濒死血细胞的内源性信号也有助于触发和/或组装酚氧化酶原激活级联反应，并且使用病毒凋亡抑制剂p35可以在体外和体内抑制这一过程。我们的结果为免疫信号转导途径提供了更全面的认识，对将细胞死亡用作细胞激活终末模式的免疫反应具有启示意义。
