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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Therapeutic effect of Lipoxin A(4)in malaria-induced acute lung injury

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Autor(es):
Padua, Tatiana A. [1, 2] ; Torres, Natalia D. [1, 2] ; Candea, Andre L. P. [1, 2] ; Souza Costa, Maria Fernanda [1, 2] ; Silva, Johnatas D. [3] ; Silva-Filho, Joao Luiz [4] ; Costa, Fabio T. M. [4] ; Rocco, Patricia R. M. [3] ; Souza, Mariana C. [1, 2] ; Henriques, Maria G. [1, 2]
Número total de Autores: 10
Afiliação do(s) autor(es):
[1] Fundacao Oswaldo Cruz, Lab Appl Pharmacol, Farmanguinhos, Rio De Janeiro - Brazil
[2] Fiocruz MS, Natl Inst Sci & Technol Innovat Dis Neglected Pop, Rio De Janeiro - Brazil
[3] Univ Fed Rio de Janeiro, Carlos Chagas Filho Inst Biophys, Lab Pulm Invest, Rio De Janeiro - Brazil
[4] Univ Campinas UNICAMP, Dept Genet Evolut & Bioagents, Inst Biol, Lab Trop Dis Prof Dr Luiz Jacintho da Silva, Campinas, SP - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: Journal of Leukocyte Biology; v. 103, n. 4, p. 657-670, APR 2018.
Citações Web of Science: 2
Resumo

Acute lung injury (ALI) models are characterized by neutrophil accumulation, tissue damage, alteration of the alveolar capillary membrane, and physiological dysfunction. Lipoxin A(4)(LXA(4)) is an anti-inflammatory eicosanoid that was demonstrated to attenuate lipopolysaccharide-induced ALI. Experimental models of severe malaria can be associated with lung injury. However, to date, a putative effect of LXA(4)on malaria (M)-induced ALI has not been addressed. In this study, we evaluated whether LXA(4) exerts an effect on M-ALI. Male C57BL/6 mice were randomly assigned to the following five groups: noninfected; saline-treatedPlasmodium berghei-infected; LXA(4)-pretreated P. berghei-infected (LXA(4)administered 1 h before infection and daily, from days 0 to 5 postinfection),LXA(4)- and LXA(4) receptor antagonist BOC-2-pretreated P. berghei-infected; and LXA(4)-posttreatedP. berghei-infected (LXA(4)administered from days 3 to 5 postinfection).By day 6, pretreatment or posttreatment with LXA(4)ameliorate lung mechanic dysfunction reduced alveolar collapse, thickening and interstitial edema;impaired neutrophil accumulation in the pulmonary tissue and blood;and reduced the systemic production of CXCL1.Additionally,in vitro treatment with LXA(4) prevented neutrophils from migrating toward plasma collected fromP. berghei-infected mice. LXA(4)also impaired neutrophil cytoskeleton remodeling by inhibiting F-actin polarization. Ex vivoanalysis showed that neutrophils from pretreated and posttreated mice were unable to migrate. In conclusion, we demonstrated that LXA(4)exerted therapeutic effects in malaria-induced ALI by inhibiting lung dysfunction, tissue injury, and neutrophil accumulation in lung as well as in peripheral blood. Furthermore, LXA(4) impaired the migratory ability of P. berghei-infected mice neutrophils. (AU)

Processo FAPESP: 16/12855-9 - Mecanismo de ação da lipoxina na proteção do desenvolvimento da malária cerebral experimental
Beneficiário:João Luiz da Silva Filho
Linha de fomento: Bolsas no Brasil - Pós-Doutorado