title: A blood fluke serine protease inhibitor regulates an endogenous larval elastase.
abstract: The larvae of Schistosoma mansoni invade their mammalian host by utilizing a serine protease, cercarial elastase (SmCE), to degrade macromolecular proteins in host skin. The catalytic activity of serine and cysteine proteases can be regulated after activation by serpins. SmSrpQ, one of two S. mansoni serpins found in larval secretions, is only expressed during larval development and in the early stages of mammalian infection. In vitro, (35)S-SmSrpQ was able to form an SDS-stable complex with a component of the larval lysate, but no complex was detected when (35)S-SmSrpQ was incubated with several mammalian host proteases. Formation of a complex was sensitive to the protease active site inhibitors PMSF, Z-AAPF-CMK, and Z-AAPL-CMK. Western blot analysis of parasite lysates from different life stages detected a complex of comparable size to SmCE bound to SmSrpQ using anti-SmSrpQ or anti-SmCE antibodies. SmSrpQ and SmCE are located in adjacent but discrete compartments in the secretion glands of the parasite. Fluorescence immunohistochemical analysis of simulated infection showed co-localization of SmCE and SmSrpQ in host tissue suggesting a post release regulation of parasite protease activity during skin transversal. The results of this study suggest that cercarial elastase degradation of skin tissue is carefully regulated by SmSrpQ.
authors.affiliation: Biomedical Science Graduate Program, University of California, San Francisco, California 94158, USA.
authors.forename: Landys A
authors.initials: L
authors.lastname: Lopez Quezada
authors.forename: Mohammed
authors.initials: M
authors.lastname: Sajid
authors.forename: Kee C
authors.initials: KC
authors.lastname: Lim
authors.forename: James H
authors.initials: JH
authors.lastname: McKerrow
mesh_terms: D000818:Animals; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry / Q000378:metabolism*; D015801:Helminth Proteins / Q000737:chemistry / Q000378:metabolism*; D006790:Host-Parasite Interactions / Q000502:physiology*; D007814:Larva / Q000378:metabolism; D008322:Mammals / Q000469:parasitology; D012550:Schistosoma mansoni / Q000502:physiology*; D012555:Schistosomiasis mansoni / Q000378:metabolism* / Q000473:pathology; D015843:Serpins / Q000737:chemistry / Q000378:metabolism*; D012908:Snails / Q000469:parasitology
chemical_list: D015853:Cysteine Proteinase Inhibitors; D015801:Helminth Proteins; D015843:Serpins