Interaction of Leptospira interrogans with Human Proteolytic Systems Enhances Dissemination through Endothelial Cells and Protease Levels

Interaction of Leptospira interrogans with Human Proteolytic Systems Enhances Dissemination through Endothelial Cells and Protease Levels

Autor Vieira, Monica L. Google Scholar
Alvarez-Flores, Miryam P. Google Scholar
Kirchgatter, Karin Google Scholar
Romero, Eliete C. Google Scholar
Alves, Ivy J. Google Scholar
Morais, Zenaide M. de Google Scholar
Vasconcellos, Silvio A. Google Scholar
Chudzinski-Tavassi, Ana M. Autor UNIFESP Google Scholar
Nascimento, Ana Lucia Tabet Oller do Google Scholar
Instituição Inst Butantan
Universidade de São Paulo (USP)
Adolfo Lutz Inst
Universidade Federal de São Paulo (UNIFESP)
Resumo We have recently reported the ability of Leptospira to capture plasminogen (PLG) and generate plasmin (PLA) bound on the microbial surface in the presence of exogenous activators. in this work, we examined the effects of leptospiral PLG binding for active penetration through the endothelial cell barrier and activation. the results indicate that leptospires with PLG association or PLA activation have enhanced migration activity through human umbilical vein endothelial cell (HUVEC) monolayers compared with untreated bacteria. Leptospira cells coated with PLG were capable of stimulating the expression of PLG activators by HUVECs. Moreover, leptospires endowed with PLG or PLA promoted transcriptional upregulation matrix metalloprotease 9 (MMP-9). Serum samples from patients with confirmed leptospirosis showed higher levels of PLG activators and total MMP-9 than serum samples from normal (healthy) subjects. the highest level of PLG activators and total MMP-9 was detected with microscopic agglutination test (MAT)-negative serum samples, suggesting that this proteolytic activity stimulation occurs at the early stage of the disease. Furthermore, a gelatin zymography profile obtained for MMPs with serum samples from patients with leptospirosis appears to be specific to leptospiral infection because serum samples from patients with unrelated infectious diseases produced no similar degradation bands. Altogether, the data suggest that the Leptospira-associated PLG or PLA might represent a mechanism that contributes to bacterial penetration of endothelial cells through an activation cascade of events that enhances the proteolytic capability of the organism. To our knowledge, this is the first proteolytic activity associated with leptospiral pathogenesis described to date.
Idioma Inglês
Data 2013-05-01
Publicado em Infection and Immunity. Washington: Amer Soc Microbiology, v. 81, n. 5, p. 1764-1774, 2013.
ISSN 0019-9567 (Sherpa/Romeo, fator de impacto)
Editor Amer Soc Microbiology
Extensão 1764-1774
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000317582700038

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