Review The Functions of Deoxyribonuclease II in Immunity and Development Ma-feng Liu, 1 Xiu-ping Wu, 1 Xue-lin Wang, 1 Yan-ling Yu, 1 Wei-fang Wang, 1 Qi-jun Chen, 1,2 Pascal Boireau, 1,3 and Ming-yuan Liu 1 Apoptosis, which is usually accompanied by DNA degradation, is important not only for the homeostasis of metazoans but also for mammalian development. If DNA is not properly degraded in these processes, it can cause diverse diseases, such as anemia, cataracts, and some autoimmune diseases. A large effort has been made to identify these nucleases that are responsible for these effects. In contrast to Deoxyribonuclease I (DNase I), Deoxyribonuclease II (DNase II) has been less well characterized in these processes. Additionally, enzymes of DNase II family in Trichinella spiralis, which is an intracellular parasitic nematode, are also considered involved in the development of the nematode. We have compiled information from studies on DNase II from various organisms and found some nonclassic features in these enzymes of T. spiralis. Here we have reviewed the characterization and functions of DNase II in these processes and predicted the functions of these enzymes in T. spiralis during host invasion and development. Introduction D Nase II are classified into a unique family of nucle- ases and have been implicated in many processes in the cell. Different from most nucleases, these enzymes do not re- quire divalent cations and may have an acidic pH optimum (Bernardi, 1971; Evans et al., 2003; MacLea et al., 2003). Zinc and copper have strong inhibitory effects on DNase II activity (Bernardi, 1971; Hevelone et al., 1988; Lyon et al., 1997). Ad- ditionally, certain monovalent cations, such as sodium, also have inhibitory effects on these enzymes at strikingly high concentrations. DNase II are expressed in a ubiquitous tissue during development and localized subcellularly in lysosomes (Liao et al., 1989). However, they are also found in nuclear fractions (Barry et al., 1993). It may be that DNase II is activated in lysosomes and transferred to nuclei to degrade DNA. In humans and rodents, three acidic DNase II have been identified: DNase IIa (Baker et al., 1998; Krieser et al., 1998), DNase IIb (Shiokawa et al., 1999), and L-DNase II (Torriglia et al., 1998). Among the three acidic DNase II, DNase IIa and DNase IIb belong to a DNase II family; DNase IIb shares 34.4% identity with DNase IIa (Shiokawa et al., 1999); and L-DNase II has some similar features when compared with DNase IIa or DNase IIb. DNase IIa and L-DNase II were ubiquitously expressed in all the tissues examined. However, DNase IIb had a more restricted pattern of expression that varies by organism, and DNase IIb activity was observed over a broader pH range (including both acidic and neutral pH) than was DNase IIa (Counis et al., 2006). L-DNase II derives from leukocyte elastase inhibitor (LEI) and exhibits a serine protease inhibitor activity and a cyto- plasmic localization. The LEI undergoes a posttranslational modification involving a shift in its molecular weight during apoptosis (from 42 kDa for the native form to 35 kDa for the cleaved form and to 27 kDa for the fully mature DNase) (Torriglia, 2003). The LEI=L-DNase II pathway may be acti- vated depending on the activation of serine proteases or may be light induced (Belmokhtar et al., 2000; Altairac et al., 2003; Chahory et al., 2004). After LEI is activated, its antiprotease activity is abolished and it exposes an endonuclease active site and a nuclear localization signal (Padron-Barthe et al., 2007). However, certain serine protease inhibitors also can inhibit apoptosis, such as the viral serpin Crm A that inhibits Fas or TNFa-induced apoptosis (Bird et al., 1998). It has been sug- gested that LEI acts as a molecular switch between life and death through apoptosis (Padron-Barthe et al., 2007). 1 Key Laboratory of Zoonosis, Institute of Zoonosis, Jilin University, Ministry of Education, Changchun, P. R. China. 2 Swedish Institute for Infectious Diseases Control, Stockholm, Sweden. 3 AFSSA, INRA, ENVA, UPVM, UMR 956 BIPAR, AFSSA LERPAZ, Maisons Alfort, France. DNA AND CELL BIOLOGY Volume 27, Number 5, 2008 ª Mary Ann Liebert, Inc. Pp. 223–228 DOI: 10.1089=dna.2007.0691 223