The effect of DMSA-functionalized magnetic nanoparticles on transendothelial migration of monocytes in the murine lung via a beta(2) integrin-dependent pathway
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
20/10/2012
20/10/2012
2010
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Resumo |
Magnetic nanoparticles surface-functionalized with meso-2,3-dimercaptosuccinic acid (MNPs-DMSA) constitute an innovative and promising approach for tissue- and cell-targeted delivery of therapeutic drugs in the lung. Transendothelial migration of leukocytes in the lung is a side effect of endovenous administration of MNPs-DMSA. Using cytologic and phenotypic analysis of murine bronchoalveolar lavage cells, we identified monocytes/macrophages as the main subpopulation of leukocytes involved in this process. Moreover, ultrastructural analysis revealed the presence of nanoparticles inside of numerous macrophages from bronchoalveolar lavage. MNPs-DMSA at concentrations as high as 1 X 10(15) nanoparticles/mL had no toxic effects on macrophages, as evidenced by 3-(4, 5-dimethylthiazolyi-2)-2,5-diphenyltetrazolium bromide (MTT) assay. Notably, MNPs-DMSA up-regulated the mRNA expression of E, L- and P-selectin and macrophage-1 antigen in the murine lung. Upregulation of these cell adhesion molecules was associated with an increased concentration of tumor necrosis factor-alpha in lung. Finally, the critical relevance of the beta(2) integrin-dependent pathway in leukocyte transmigration elicited by MNPs-DMSA was demonstrated by use of knockout mice. Our results characterize mechanisms of the pro-inflammatory effects of MNPs-DMSA in the lung, and identify beta(2) integrin-targeted interventions as promising strategies to reduce pulmonary side effects of MNPs-DMSA during biomedical applications. (C) 2009 Elsevier Ltd. All rights reserved. MCT/CNPq Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) FINATEC FINATEC Fundação de Apoio à Pesquisa do Distrito Federal (FAPDF) FAP-DF Financiadora de Estudos e Projetos (FINEP) FINEP FUNAPE FUNAPE |
Identificador |
BIOMATERIALS, v.31, n.2, p.366-374, 2010 0142-9612 http://producao.usp.br/handle/BDPI/28052 10.1016/j.biomaterials.2009.09.053 |
Idioma(s) |
eng |
Publicador |
ELSEVIER SCI LTD |
Relação |
Biomaterials |
Direitos |
restrictedAccess Copyright ELSEVIER SCI LTD |
Palavras-Chave | #Cell adhesion #Integrin #Leukocyte #Lung #Nanoparticle #Selectin #MAGHEMITE NANOPARTICLES #NEUTROPHIL EMIGRATION #CELL-LINES #IN-VITRO #ADHESION #MICE #C3A #TRANSMIGRATION #INFLAMMATION #FIBRONECTIN #Engineering, Biomedical #Materials Science, Biomaterials |
Tipo |
article original article publishedVersion |