Abstract
Toxocara canis (T. canis), the ascarid of canids, is well known to infect noncanids, including humans and mice, and causes toxocariasis such as respiratory symptoms. Heretofore, nothing was known about the association among plasminogen activators (PAs), matrix metalloproteinases (MMPs) and the pathogenesis of T. canis infection. In the present work, we investigated the pulmonary pathological alteration and the activity of PAs and MMPs in lungs of BALB/c mice after infection with 2,000 infective embryonated eggs. A gradual increase in pathological effects after infection culminated in a severe infiltration of leukocytes and hemorrhage from days 4 to 14 post-infection (PI). Casein zymogram analysis demonstrated that 70 kDa tPA and 55 kDa uPA from the lungs at day 4 PI were active against the casein/plasminogen substrate. Gelatin zymography using substrate gelatin manifested a significant increase in the relative activity of 94 kDa MMP-9 and 68 kDa MMP-2 in T. canis -infected mice. By Western blot analysis, the protein level of 220 kDa fibronectin (FN) monomer showed a significant increase in T. canis-infected mice, compared with uninfected control. Infection with T. canis in BALB/c mice induced PAs and MMPs activity in parallel with the pathological changes of early stage pulmonary inflammation. In conclusion, we observed PAs/MMPs cascade activation in pulmonary pathogenesis caused by T. canis larva migration. Thus, murine T. canis infection may prove to be useful in understanding the role of PAs and MMPs in pulmonary inflammation.
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