title: Lagochilascaris minor third-stage larvae secrete metalloproteases with specificity for fibrinogen and native collagen.
abstract: Dissemination of parasitic infections depends on migration through tissues and evasion from both hemostatic processes and immune responses from hosts. Metalloproteases play major roles in these mechanisms of pathogen-host interactions and, thus, are considered drug targets. In this study, we characterized metalloprotease activities in excretory/secretory (ES) products from third stage larvae (L3) of the ascarid Lagochilascaris minor, the causative agent of lagochilascariosis, which demonstrates an impressive migrating capacity across host tissues, including bone. Gel enzymography showed that ES products of L3 display two major gelatinolytic activities. Optimal proteolytic activity was found to occur at neutral/alkaline pH and was associated with two L. minor-secreted metalloproteases of 59 (SM59(Lm)) and 114kDa (SM114(Lm)). We next showed that ES products of L3 were able to hydrolyze fibrinogen and collagen I at neutral pH, but not BSA, in an extensive manner. Furthermore, we demonstrated that ES products of L3 mediate hydrolysis of the triple helical structure of collagen I fibers in mouse mesentery. These results suggest that ES proteases of L3 might facilitate both L. minor migration through host tissues by hydrolyzing collagens of the extracellular matrix and evasion from host hemostatic mechanisms by degrading fibrinogen.
authors.affiliation: Laboratório de Biologia, Bioquímica e Imunologia de Helmintos, Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Setor Leste Universitário, 74605-050 Goiânia, GO, Brazil. alverne@iptsp.ufg.br
authors.forename: Alverne Passos
authors.initials: AP
authors.lastname: Barbosa
authors.forename: Dulcinéa Maria Barbosa
authors.initials: DM
authors.lastname: Campos
authors.forename: Amélia Regina
authors.initials: AR
authors.lastname: Semerene
authors.forename: Antonio R L
authors.initials: AR
authors.lastname: Teixeira
authors.forename: Jaime Martins
authors.initials: JM
authors.lastname: Santana
mesh_terms: D000818:Animals; D017191:Ascaridida Infections / Q000469:parasitology / Q000473:pathology; D001199:Ascaridoidea / Q000201:enzymology* / Q000254:growth & development; D003094:Collagen / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004795:Enzyme Stability; D005340:Fibrinogen / Q000378:metabolism*; D005780:Gelatin / Q000378:metabolism; D006651:Histocytochemistry; D006863:Hydrogen-Ion Concentration; D007814:Larva / Q000201:enzymology; D008643:Mesentery / Q000473:pathology; D045726:Metalloproteases / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D012710:Serum Albumin, Bovine / Q000378:metabolism
chemical_list: D012710:Serum Albumin, Bovine; D005780:Gelatin; D005340:Fibrinogen; D003094:Collagen; D045726:Metalloproteases