Therapeutic effect of Lipoxin A4 in malaria-induced acute lung injury.
J Leukoc Biol
; 103(4): 657-670, 2018 04.
Article
de En
| MEDLINE
| ID: mdl-29345368
ABSTRACT
Acute lung injury (ALI) models are characterized by neutrophil accumulation, tissue damage, alteration of the alveolar capillary membrane, and physiological dysfunction. Lipoxin A4 (LXA4 ) 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 LXA4 on malaria (M)-induced ALI has not been addressed. In this study, we evaluated whether LXA4 exerts an effect on M-ALI. Male C57BL/6 mice were randomly assigned to the following five groups noninfected; saline-treated Plasmodium berghei-infected; LXA4 -pretreated P. berghei-infected (LXA4 administered 1 h before infection and daily, from days 0 to 5 postinfection), LXA4 - and LXA4 receptor antagonist BOC-2-pretreated P. berghei-infected; and LXA4 -posttreated P. berghei-infected (LXA4 administered from days 3 to 5 postinfection). By day 6, pretreatment or posttreatment with LXA4 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 LXA4 prevented neutrophils from migrating toward plasma collected from P. berghei-infected mice. LXA4 also impaired neutrophil cytoskeleton remodeling by inhibiting F-actin polarization. Ex vivo analysis showed that neutrophils from pretreated and posttreated mice were unable to migrate. In conclusion, we demonstrated that LXA4 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, LXA4 impaired the migratory ability of P. berghei-infected mice neutrophils.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Plasmodium berghei
/
Mouvement cellulaire
/
Anti-inflammatoires non stéroïdiens
/
Lipoxines
/
Lésion pulmonaire aigüe
/
Paludisme
/
Granulocytes neutrophiles
Type d'étude:
Etiology_studies
Limites:
Animals
Langue:
En
Journal:
J Leukoc Biol
Année:
2018
Type de document:
Article
Pays d'affiliation:
Brésil