Author | Svensjö, Nils Erik | |
Author | Batista, Paulo Ricardo | |
Author | Brodskyn, Claudia Ida | |
Author | Silva, Robson Amaro Augusto da | |
Author | Lima, Ana Paula Cabral de Araujo | |
Author | Pereira, Verônica Schmitz | |
Author | Bou Habib, Elvira Maria Saraiva Chequer | |
Author | Pesquero, João Bosco | |
Author | Mori, Marcelo Alves da Silva | |
Author | Müller-Esterl, Werner | |
Author | Scharfstein, Julio | |
Access date | 2014-09-18T16:18:30Z | |
Available date | 2014-09-18T16:18:30Z | |
Document date | 2006 | |
Citation | SVENSJO, E. et al. Interplay between parasite cysteine proteases and the host kinin system modulates microvascular leakage and macrophage infection by promastigotes of the Leishmania donovani complex. Microbes Infection, v.8, n. 1, p. 206-220, 2006. | pt_BR |
ISSN | 1286-4579 | |
URI | https://www.arca.fiocruz.br/handle/icict/8398 | |
Language | eng | pt_BR |
Publisher | Elsevier SAS | pt_BR |
Rights | open access | pt_BR |
Title | Interplay between parasite cysteine proteases and the host kinin system modulates microvascular leakage and macrophage infection by promastigotes of the Leishmania donovani complex. | pt_BR |
Type | Article | pt_BR |
DOI | 10.1016/j.micinf.2005.06.016 | |
Abstract | Kinins, the vasoactive peptides proteolytically liberated from kininogens, were recently recognized as signals alerting the innate immune
system. Here we demonstrate that Leishmania donovani and Leishmania chagasi, two etiological agents of visceral leishmaniasis (VL),
activate the kinin system. Intravital microscopy in the hamster cheek pouch showed that topically applied promastigotes induced macromolecular
leakage (FITC-dextran) through postcapillary venules. Peaking at 15 min, the parasite-induced leakage was drastically enhanced by
captopril (Cap), an inhibitor of angiotensin-converting enzyme (ACE), a kinin-degrading metallopeptidase. The enhanced microvascular
responses were cancelled by HOE-140, an antagonist of the B2 bradykinin receptor (B2R), or by pre-treatment of promastigotes with the
irreversible cysteine proteinase inhibitor N-methylpiperazine-urea-Phe-homoPhe-vinylsulfone-benzene (N-Pip-hF-VSPh). In agreement with
the above-mentioned data, the promastigotes vigorously induced edema in the paw of Cap-treated J129 mice, but not Cap-B2R–/– mice.
Analysis of parasite-induced breakdown of high molecular weight kininogens (HK), combined with active site-affinity-labeling with biotin-
N-Pip-hF-VSPh, identified 35–40 kDa proteins as kinin-releasing cysteine peptidases.We then checked if macrophage infectivity was influenced
by interplay between these kinin-releasing parasite proteases, kininogens, and kinin-degrading peptidases (i.e. ACE). Our studies
revealed that full-fledged B2R engagement resulted in vigorous increase of L. chagasi uptake by resident macrophages. Evidence that inflammatory
macrophages treated with HOE-140 became highly susceptible to amastigote outgrowth, assessed 72 h after initial macrophage
interaction, further suggests that the kinin/B2R activation pathway may critically modulate inflammation and innate immunity in visceral
leishmaniasis. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil | pt_BR |
Affilliation | Universidade Federal do Estado de São Paulo. UNIFESP. Escola Paulista de Medicina. Departamento de Biofísica. São Paulo, SP, Brasil | pt_BR |
Affilliation | Universidade Federal do Estado de São Paulo. UNIFESP. Escola Paulista de Medicina. Departamento de Biofísica. São Paulo, SP, Brasil | pt_BR |
Affilliation | University of Frankfurt Medical School. Institute for Biochemistry II. Frankfurt, Germany | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Subject | Leishmaniasis | pt_BR |
Subject | Innate immunity | pt_BR |
Subject | Inflammation | pt_BR |
Subject | Macrophages | pt_BR |
Subject | Endothelium | pt_BR |
Subject | Kinins | pt_BR |
Subject | Angiotensin-converting enzyme | pt_BR |
Subject | Cysteine proteases | pt_BR |
DeCS | Permeabilidade Capilar/fisiologia | pt_BR |
DeCS | Cisteína Endopeptidases/metabolismo | pt_BR |
DeCS | Cininas/metabolismo | pt_BR |
DeCS | Leishmania donovani/enzimologia | pt_BR |
DeCS | Leishmania infantum/enzimologia | pt_BR |
DeCS | Macrófagos/metabolismo | pt_BR |
DeCS | Animais | pt_BR |
DeCS | Cricetinae | pt_BR |
DeCS | Deleção de Genes | pt_BR |
DeCS | Masculino | pt_BR |
DeCS | Camundongos | pt_BR |
DeCS | Camundongos Endogâmicos BALB C | pt_BR |
DeCS | Peptidil Dipeptidase A/metabolismo | pt_BR |
DeCS | Receptores da Bradicinina/genética | pt_BR |
DeCS | Receptores da Bradicinina/metabolismo | pt_BR |
DeCS | Fatores de Tempo | pt_BR |