Annexin A1 modulates natural and glucocorticoid-induced resolution of inflammation by enhancing neutrophil apoptosis

Journal of Leukocyte Biology

Juliana P. Vago, ¹  Fernando Lopes¹  Remo C. Russo¹  Frederico M. Soriani¹  Luciana P. Tavares¹  Lirlândia P. Sousa, ¹  Camila R. C. Nogueira ¹  Vanessa Pinho¹  Mauro M. Teixeira  and¹ 

[1] Programa de Pós-Graduação em Biologia Celular, Departamento de Morfologia,  Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia, and Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, and Departamento de AnÃlises Clínicas e Toxicológicas, Faculdade de FarmÃcia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

关键词: signaling cascade;    dexamethasone;    wortmannin;    rolipram;    Bcl-2 family;   

DOI  :  10.1189/jlb.0112008

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

This study aimed at assessing whether AnxA1, a downstream mediator for the anti-inflammatory effects of GCs, could affect the fate of immune cells in tissue exudates, using LPS-induced pleurisy in BALB/c mice. AnxA1 protein expression in exudates was increased during natural resolution, as seen at 48–72 h post-LPS, an effect augmented by treatment with GC and associated with marked presence of apoptotic neutrophils in the pleural exudates. The functional relevance of AnxA1 was determined using a neutralizing antibody or a nonspecific antagonist at FPR/ALXRs: either treatment inhibited both spontaneous and GC-induced resolution of inflammation. Injection of Ac2-26 (100 μg, given 4 h into the LPS response), an AnxA1-active N-terminal peptide, promoted active resolution and augmented the extent of neutrophil apoptosis. Such an effect was prevented by the pan-caspase inhibitor zVAD-fmk. Mechanistically, resolution of neutrophilic inflammation was linked to cell apoptosis with activation of Bax and caspase-3 and inhibition of survival pathways Mcl-1, ERK1/2, and NF-κB. These novel in vivo data, using a dynamic model of acute inflammation, provide evidence that AnxA1 is a mediator of natural and GC-induced resolution of inflammation with profound effects on neutrophil apoptosis.

【 授权许可】

Unknown