title: Surface-displayed glyceraldehyde 3-phosphate dehydrogenase and galectin from Dirofilaria immitis enhance the activation of the fibrinolytic system of the host.
abstract: Cardiopulmonary dirofilariosis is a cosmopolitan disease caused by Dirofilaria immitis, a filaroid parasite whose adult worms live for years in the vascular system of its host. Previous studies have shown that D. immitis can use their excretory/secretory (ES) and surface antigens to enhance fibrinolysis, which could limit the formation of clots in its surrounding environment. Moreover, several isoforms of the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and galectin (GAL) were identified in both antigenic extracts as plasminogen-binding proteins. The aim of this work is to study the interaction of the GAPDH and GAL of D. immitis with the fibrinolytic system of the host. This study includes the cloning, sequencing and expression of the recombinant forms of the GAPDH and GAL of D. immitis (rDiGAPDH and rDiGAL) and the analysis of their capacity as plasminogen-binding proteins. The results indicate that rDiGAPDH and rDiGAL are able to bind plasminogen and stimulate plasmin generation by tissue plasminogen activator (tPA). This interaction needs the involvement of lysine residues, many of which are located externally in both proteins as have been shown by the molecular modeling of their secondary structures. In addition, we show that rDiGAPDH and rDiGAL enhance the expression of the urokinase-type plasminogen activator (uPA) on canine endothelial cells in culture and that both proteins are expressed on the surface of D. immitis in close contact with the blood of the host. These data suggest that D. immitis could use the associated surface GAPDH and GAL as physiological plasminogen receptors to shift the fibrinolytic balance towards the generation of plasmin, which might constitute a survival mechanism to avoid the clot formation in its intravascular habitat.
authors: Faculty of Pharmacy, Laboratory of Parasitology, Institute of Biomedical Research of Salamanca (IBSAL), University of Salamanca, 37007 Salamanca, Spain. Electronic address: jglez@usal.es.
authors: Javier
authors: J
authors: González-Miguel
authors: Faculty of Pharmacy, Laboratory of Parasitology, Institute of Biomedical Research of Salamanca (IBSAL), University of Salamanca, 37007 Salamanca, Spain.
authors: Rodrigo
authors: R
authors: Morchón
authors: Laboratory of Parasitology, IRNASA, CSIC, Salamanca, Spain.
authors: Mar
authors: M
authors: Siles-Lucas
authors: Laboratory of Parasitology, IRNASA, CSIC, Salamanca, Spain.
authors: Ana
authors: A
authors: Oleaga
authors: Faculty of Pharmacy, Laboratory of Parasitology, Institute of Biomedical Research of Salamanca (IBSAL), University of Salamanca, 37007 Salamanca, Spain.
authors: Fernando
authors: F
authors: Simón
mesh_terms: D000328:Adult; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D004183:Dirofilaria immitis / Q000201:enzymology*; D004285:Dogs / Q000469:parasitology*; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis / Q000502:physiology*; D037161:Galectins / Q000378:metabolism*; D005986:Glyceraldehyde 3-Phosphate / Q000378:metabolism*; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism; D006790:Host-Parasite Interactions / Q000502:physiology*; D006801:Humans; D010958:Plasminogen / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D037161:Galectins; D015801:Helminth Proteins; D005986:Glyceraldehyde 3-Phosphate; D010958:Plasminogen; D005341:Fibrinolysin
keywords: Dirofilaria immitis; Fibrinolysis; Galectin; Glyceraldehyde 3-phosphate dehydrogenase; Plasminogen