title: Glyceraldehyde 3-phosphate dehydrogenase and galectin from Dirofilaria immitis participate in heartworm disease endarteritis via plasminogen/plasmin system.
abstract: The interaction between parasitic protozoa and helminths, both in the blood and in tissues and the fibrinolytic system of their hosts is usually considered as a survival parasite mechanism since this system is the physiological route responsible for degrading fibrin clots. The broad-range proteolytic activity of plasmin, the final enzyme of the route, implies that its recruitment by these parasites is an important mechanism that mediates their invasion and establishment in the hosts. However, recent studies have proposed a dual role for plasmin by linking its over-production with pathological mechanisms at vascular level. Most of these studies have been conducted in Dirofilaria immitis, a blood-borne parasite that survives in the pulmonary arteries of its host for years while it produces a chronic inflammatory disease, whose main pathogenic mechanism is the appearance of proliferative endarteritis. Recently, the participation of two proteins from D. immitis, glyceraldehyde 3-phosphate dehydrogenase (DiGAPDH) and galectin (DiGAL), in the activation of the fibrinolytic system of its host has been demonstrated, which has been a priori associated with parasite survival mechanisms. The aim of the present paper was to study the role of plasmin generated by these proteins in the emergence of proliferative endarteritis. An in vitro model of canine endothelial and smooth muscle cells, as well as the two parasitic recombinant proteins were employed. The results show that DiGAPDH and DiGAL stimulate the proliferation and migration of both cell types, as well as the degradation of the extracellular matrix (ECM) via plasminogen (PLG)/plasmin system, being all of these mechanisms related to the appearance of proliferative endarteritis. Due to the high degree of evolutionary conservation of these antigens, these data support the hypothesis of the survival/pathology ambivalence in the interactions between parasites and the fibrinolytic system of their hosts and represent an advance in the knowledge of the mechanisms involved in the emergence of proliferative endarteritis in the cardiopulmonary dirofilariosis (heartworm disease).
authors.affiliation: Laboratory of Parasitology, Faculty of Pharmacy, University of Salamanca, Salamanca, Spain. Electronic address: jglez@usal.es.
authors.forename: Javier
authors.initials: J
authors.lastname: González-Miguel
authors.affiliation: Laboratory of Parasitology, Faculty of Pharmacy, University of Salamanca, Salamanca, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Larrazabal
authors.affiliation: Laboratory of Parasitology, Faculty of Pharmacy, University of Salamanca, Salamanca, Spain.
authors.forename: Diana
authors.initials: D
authors.lastname: Loa-Mesón
authors.affiliation: Laboratory of Parasitology, IRNASA, CSIC, Salamanca, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Siles-Lucas
authors.affiliation: Laboratory of Parasitology, Faculty of Pharmacy, University of Salamanca, Salamanca, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Simón
authors.affiliation: Laboratory of Parasitology, Faculty of Pharmacy, University of Salamanca, Salamanca, Spain.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Morchón
mesh_terms: D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D004183:Dirofilaria immitis / Q000235:genetics / Q000378:metabolism*; D004184:Dirofilariasis / Q000469:parasitology*; D004283:Dog Diseases / Q000469:parasitology; D004285:Dogs; D042783:Endothelial Cells / Q000502:physiology; D005341:Fibrinolysin / Q000378:metabolism*; D037161:Galectins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism*
chemical_list: D037161:Galectins; D010958:Plasminogen; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D005341:Fibrinolysin
keywords: Dirofilaria immitis; Fibrinolysis; Galectin; Glyceraldehyde 3-phosphate dehydrogenase; Plasmin; Proliferative endarteritis