Vascular endothelial cell activation by adult Dirofilaria immitis antigens.
Dirofilaria immitis is the causal agent of cardiopulmonary dirofilariosis (heartworm disease). Adult worms lodge in the pulmonary arteries and right ventricle, thus vascular endothelium is exposed to high concentrations of Dirofilaria antigenic products. Heartworm disease habitually develops as a chronic foreseeable pathology. Moreover, the simultaneous death of many adult worms, naturally or induced by a filaricide treatment, can cause acute thromboembolisms and endarteritis. To better understand the effects of the massive death of D. immitis adult worms on the blood vessel endothelium, we cultured vascular endothelial cells in the presence or absence of an antigenic extract of D. immitis adult worms (DiSA). The parasite products increased the expression of enzymes and the synthesis of eicosanoids related to inflammation, such as COX-2, 5-LO, PGE(2) and LTB(4). The expression of ICAM-1 and PECAM-1 adhesion molecules and endothelial and inducible Nitric Oxide Synthases (eNOS and iNOS) was also increased in cultures treated with DiSA. Nevertheless, DiSA decreased endothelial permeability and does not alter both proliferation and apoptosis. These results suggest that the somatic extract of D. immitis adult worms stimulate inflammatory mechanisms in endothelial cells, without altering their basic physiologic processes.
Morchón
R
R
Laboratorio de Parasitología, Facultad de Farmacia, Universidad de Salamanca, Avda. del Campo Charro s/n, 37007 Salamanca, Spain.
Rodríguez-Barbero
A
A
Velasco
S
S
López-Belmonte
J
J
Simón
F
F
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D004183:Dirofilaria immitis / Q000276:immunology / Q000472:pathogenicity*; D004184:Dirofilariasis; D015777:Eicosanoids / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology* / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*
D000947:Antigens, Helminth; D015777:Eicosanoids; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019001:Nitric Oxide Synthase