Expression Patterns of Cell Adhesion Molecules in Mice's Lung After Administration of Meso-2,3-Dimercaptosuccinic Acid-Coated Maghemite Nanoparticles

Abstract

We studied the expression pattern of cell adhesion molecules associated to transendothelial migration of leukocytes in different lung's vascular compartments after administration of a magnetic fluid sample containing maghemite nanoparticles surface-coated with meso-2,3-dimercaptosuccinic acid. The analyses were conducted in mice 4 and 12 h after endovenous administration of the magnetic fluid in control mice. Firstly, the migratory activity of leukocytes after magnetic fluid surface-coated with meso-2,3-dimercaptosuccinic acid administration was confirmed using broncho-alveolar lavage and light microscopy. Then, the expression of cell adhesion molecules in the lung's vascular compartments was investigated by immunofluorescence microscopy of frozen sections, using antibodies against L-selectin, P-selectin, E-selectin, macrophage antigen-1, and leukocyte function associated antigen-1. L- and P-selectin showed similar pattern of expression in the pulmonary vasculature in animals treated with magnetic fluid and in the control group. In contrast, macrophage antigen-1 and leukocyte function associated antigen-1 were found in capillary only in animals treated with magnetic fluid surface-coated with meso-2,3-dimercaptosuccinic acid administration. In addition, after magnetic fluid administration E-selectin was found in post-capillary sites. Our findings demonstrated that magnetic fluid surface-coated with meso-2,3-dimercaptosuccinic acid administration exhibits modulation effects on expression patterns of E-selectin, macrophage antigen-1, and leukocyte function associated antigen-1 in the lung's vascular compartments. These findings are very important in a strategy to reduce the potential toxicity of magnetic fluid surface-coated with meso-2,3-dimercaptosuccinic acid administration for medical applications.

The effect of DMSA-functionalized magnetic nanoparticles on transendothelial migration of monocytes in the murine lung via a β2 integrin-dependent pathway

“…In this case, both LFA-1 and VLA-4 could play a functional role in the process of transendothelial migration of monocytes induced by MNPs-DMSA. Supporting this perspective, we have previously shown that MNPs-DMSA modulate the expression pattern of LFA-1 on leukocytes located in the vascular compartment of the lung [6]. Conversely, the absence of a significant change in the mRNA expression of VCAM-1 (Fig.…”

“…While MNPs-DMSA has been shown to cause transendothelial migration of leukocytes into the lung [4][5][6], the time course of this process is still unclear. In the present study, we detected a timedependent increase in the number of leukocytes in bronchoalveolar lavage fluid within the first 12 h after administration of MNPs-DMSA as compared to controls (P < 0.05; Fig.…”

“…Since blockade of integrins by antibodies and/ or receptor-based antagonists can interfere with the ability of leukocytes to extravasate in vivo [48], the above results identify b 2 integrin-inhibitors as a promising therapeutic strategy to prevent or minimize the pro-inflammatory effects of MNPs-DMSA during biomedical applications in the lung. Indeed, the evident pro-inflammatory effects of MNPs-DMSA [4][5][6] raise concern as to their use in humans. However, we consider the diagnostic and therapeutic potential of MNPs-DMSA so promising and broad in application that it outweighs by far this disadvantage, provided that tools can be developed to reduce the pro-inflammatory side effects to a minimum.…”

“…In a recent study we proposed that a possible mechanism by which MNPs-DMSA induce transendothelial migration of leukocytes into the lung is based on their ability to modulate the expression of cell adhesion molecules on leukocytes and lung vascular endothelial cells [6]. In order to test this hypothesis in the present study, we first analyzed the time profile of leukocyte migration into the airspaces following MNPs-DMSA administration and the subpopulation of leukocytes involved in this process.…”

“…This target specificity of MNPs-DMSA offers a unique property which may be successfully exploited for the treatment of lung diseases, in that comparably high doses of drugs can be delivered to the lung without increasing side effects in extrapulmonary organs [3]. However, MNPs-DMSA cause transendothelial migration of leukocytes from blood vessels into the lung parenchyma or airspace [4][5][6]. Leukocyte accumulation in the extravascular compartments of the lung may cause tissue injury by excessive release of toxic substances, including proteases and reactive oxygen species [7,8], and thus constitutes a potentially harmful side effect of MNPs-DMSA in the lung during clinical applications.…”