Therapeutic Effect Of Lipoxin A(4)In Malaria-Induced Acute Lung Injury
JOURNAL OF LEUKOCYTE BIOLOGY(2018)
摘要
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.
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关键词
cytoskeleton remodeling, lung, LXA(4) receptor, Plasmodium berghei, specialized proresolving mediators
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