Therapeutic effect of lipoxin A4 in malaria‐induced acute lung injury

Pádua, T. A., Torres, N. D., Candéa, A. L. P., Costa, M. F. S., Silva, J. D., Silva‐Filho, J. L. , Costa, F. T. M., Rocco, P. R. M., Souza, M. C. and Henriques, M. G. (2018) Therapeutic effect of lipoxin A4 in malaria‐induced acute lung injury. Journal of Leukocyte Biology, 103(4), pp. 657-670. (doi: 10.1002/JLB.3A1016-435RRR) (PMID:29345368)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Da Silva Filho, Dr Joao
Authors: Pádua, T. A., Torres, N. D., Candéa, A. L. P., Costa, M. F. S., Silva, J. D., Silva‐Filho, J. L., Costa, F. T. M., Rocco, P. R. M., Souza, M. C., and Henriques, M. G.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Journal of Leukocyte Biology
Publisher:Wiley
ISSN:0741-5400
ISSN (Online):1938-3673
Published Online:03 January 2018

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