Matrix metalloproteinases with gelatinolytic activity induced by Paracoccidioides brasiliensis infection.
Matrix metalloproteinases (MMPs) modulate extracellular matrix turnover, inflammation and immunity. We studied MMP-9 and MMP-2 in experimental paracoccidioidomycosis. At 15 and 120 days after infection (DAI) with virulent Paracoccidioides brasiliensis, MMP-9 was positive by immunohistochemistry in multinucleated giant cells, in mononuclear cells with macrophage and lymphocyte morphologies and also in fungal cells in the lesions of susceptible and resistant mice. Using gelatin zymography, pro- and active MMP-9 and active MMP-2 were detected in all infected mice, but not in controls. Gelatinolytic activity was not observed in P. brasiliensis extracts. Semiquantitative analysis of gelatinolytic activities revealed weak or absent MMP-2 and strong MMP-9 activity in both mouse strains at 15 DAI, declining at 120 DAI. Avirulent P. brasiliensis-infected mice had residual lesions with MMP-9-positive pseudoxantomatous macrophages, but no gelatinase activity at 120 DAI. Our findings demonstrate the induction of MMPs, particularly MMP-9, in experimental paracoccidioidomycosis, suggesting a possible influence in the pattern of granulomas and in fungal dissemination.
Nishikaku
Angela Satie
AS
Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, SP, Brazil.
Ribeiro
Luciana Cristina
LC
Molina
Raphael Fagnani Sanchez
RF
Albe
Bernardo Paulo
BP
Cunha
Cláudia da Silva
Cda S
Burger
Eva
E
D000818:Animals; D005260:Female; D005780:Gelatin / Q000378:metabolism; D006099:Granuloma / Q000201:enzymology / Q000382:microbiology; D007124:Immunoenzyme Techniques; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009852:Omentum / Q000201:enzymology; D010228:Paracoccidioides; D010229:Paracoccidioidomycosis / Q000201:enzymology*; D010532:Peritoneal Diseases / Q000201:enzymology / Q000382:microbiology
D005780:Gelatin; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9