5-lipoxygenase pathway is essential for the control of granuloma extension induced by Schistosoma mansoni eggs in lung.
According to WHO, it is estimated that approximately 2 billion people are infected with intestinal helminths worldwide and the number of people who are cured of these diseases is relatively low, resulting in a large percentage of chronically infected individuals. Schistosomiasis is one of the most important parasitic diseases present in developing countries configuring it as a serious public health problem, directly related to poverty and social disadvantage. Once the parasite infection is established, Schistosoma mansoni eggs fall into the bloodstream and are trapped in the liver microcirculation where a strong granulomatous response and fibrosis formation occurs. In the experimental model, granulomas develop in the mouse lung after intravenous injection of purified eggs. Here we aim to understand how leukotrienes are involved in the granuloma formation. Leukotrienes are lipid mediators derived from arachidonic acid metabolites via 5-lipoxygenase (5LO) enzyme. They are potent proinflammatory agents and induce recruitment, cell activation, regulation of microbicidal activity of polymorphonuclear and mononuclear cells. In this study, 5LO deficient mice (5LO(-/-)) were inoculated with S. mansoni eggs for evaluation of immunopathological parameters involved in the induction of type 2 granulomas. We showed that in the absence of leukotrienes, the size of granulomas were decreased comparing to the wild type mice and the inflammatory compromised areas had a lower extension. In 5LO(-/-) mice granulomas presented extensive areas of fibrosis, detected by α-SMA expression along the lesions, indicating remodeling in attempt to reestablish the normal tissue. Also, comparing to WT mice we detected decrease of IL-4 and IL-13 and increase of TGF-β in the lung of 5LO(-/-), but these mice failed to produce protective IFN-γ and IL-12. These results evidenced 5-Lipoxygenase as an important pathway during lung injury due to Schistosoma-eggs injection.
Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Av do Cafe s/n, Ribeirao Preto, SP, Brazil. Electronic address: gabriel.toffoli.silva@usp.br.
Gabriel
G
Toffoli da Silva
Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Av do Cafe s/n, Ribeirao Preto, SP, Brazil. Electronic address: milenasespindola@gmail.com.
Milena Sobral
MS
Espíndola
Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Av do Cafe s/n, Ribeirao Preto, SP, Brazil. Electronic address: fontanari@usp.br.
Caroline
C
Fontanari
Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Av do Cafe s/n, Ribeirao Preto, SP, Brazil.
Rogerio Silva
RS
Rosada
Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Av do Cafe s/n, Ribeirao Preto, SP, Brazil.
Lúcia Helena
LH
Faccioli
Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Av dos Bandeirantes, 1900, Ribeirao Preto, SP, Brazil. Electronic address: sgramos@fmrp.usp.br.
Simone Gusmão
SG
Ramos
Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Av dos Bandeirantes, 1900, Ribeirao Preto, SP, Brazil. Electronic address: vrodrigu@fmrp.usp.br.
Vanderlei
V
Rodrigues
Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Av do Cafe s/n, Ribeirao Preto, SP, Brazil. Electronic address: frantz@usp.br.
Fabiani Gai
FG
Frantz
D000199:Actins / Q000032:analysis; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D001700:Biomphalaria; D006099:Granuloma / Q000469:parasitology / Q000473:pathology*; D015289:Leukotrienes / Q000378:metabolism; D008168:Lung / Q000469:parasitology* / Q000473:pathology; D008174:Lung Diseases, Parasitic / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010063:Ovum / Q000502:physiology; D012550:Schistosoma mansoni / Q000502:physiology*; D012555:Schistosomiasis mansoni / Q000473:pathology*; D015398:Signal Transduction
D000199:Actins; D015289:Leukotrienes; C544013:alpha-smooth muscle actin, mouse; D001094:Arachidonate 5-Lipoxygenase
5-Lipoxygenase; Leukotrienes; Shistosoma mansoni; Type-2 granuloma