Leukocyte transepithelial migration in lung induced by DMSA functionalized magnetic nanoparticles

作者:Azevedo Ricardo Bentes*; Alves Valois Caroline Rodrigues; Chaves Sacha Braun; Silva Jaqueline Rodrigues; Garcia Monica Pereira
来源:Cell Adhesion and Migration, 2011, 5(1): 29-33.
DOI:10.4161/cam.5.1.13558

摘要

Magnetic nanoparticles surface-covered with meso-2,3-dimercaptosuccinic acid (MNPs-DMSA) constitute a promising approach for tissue- and cell-targeted delivery of therapeutic drugs in the lung. However, they can also induce a transient transendothelial migration of leukocytes in the organ as a side effect after endovenous administration of MNPs-DMSA. We demonstrated that monocytes/macrophages constitute the main subpopulation of leukocytes involved in this process. Our recent research found that MNPs-DMSA upregulated the mRNA expression of E-, L-and P-selectin and macrophage-1 antigen and increased concentration of tumor necrosis factor alpha (TNF alpha) in lung, in a time dependent manner. 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 work characterizes mechanisms of the pro-inflammatory effects of MNPs-DMSA in the lung and identifies beta(2) integrin-targeted interventions as promising strategies to reduce pulmonary side effects of MNPs-DMSA during biomedical applications. In addition, MNPs-DMSA could be used as modulators of lung immune response.

  • 出版日期2011-2