Changes in lung immune cell infiltrates after electric field treatment in mice

Abstract

Exogenous electric fields are currently used in human therapy in a number of contexts. Interestingly, electric fields have also been shown to alter migration and function of immune cells, suggesting the potential for electric field-based immune therapy. Little is known as to the effect of electric field treatment (EFT) on the lung. To determine if EFT associates with changes in lung immune cell infiltration, we used a mouse model with varying methods of EFT application and measured cells and soluble mediators using flow cytometry and cytokine/chemokine multiplex. EFT was associated with a transient increase in lung neutrophils and decrease in eosinophils in naïve mice within 2 h of treatment, accompanied by an increase in IL-6 levels. In order to test whether EFT could alter eosinophil/neutrophil recruitment in a relevant disease model, a mouse model of allergic airway inflammation was used. Four EFT doses in allergen-sensitized mice resulted in increased neutrophil and reduced eosinophil infiltrates following allergen challenge, suggesting a durable change in inflammation by EFT. Mice with allergic inflammation were analyzed by flexiVent for measures of lung function. EFT-treated mice had increased inspiratory capacity and other measures of lung function were not diminished. These data suggest EFT may be used to manipulate immune cell infiltration in the lung without affecting lung function.

Electrotaxis of alveolar epithelial cells in direct-current electric fields

“…Nonetheless, the impacts of EFs on lung injury repair are complex. A recent study showed that applying EFs could result in a transient increase in lung neutrophils and a decrease in eosinophils, accompanied by an increase in IL-6 levels, 20 and an early study demonstrated that neutrophils could help repair airway epithelium by removal of injured epithelial cells. 21 Furthermore, a recent study stated that EFs could guide the directional migration of T cells to the cathode, but significantly decrease T-cell activation, and remarkably dampen CD4 (+) T-cell polarization.…”

Gene Therapy for Acute Respiratory Distress Syndrome

“…Additionally, EP does not induce any immune response, which is a significant safety concern in viral vector delivery system. However, a recent report indicated that a small transient increase in neutrophils could be detected in the lungs of mice within the first hour of electroporation, but that this returned to normal within 24 h; whether this has any lasting effects is unknown at this point, but, given that EP has been used by multiple groups to treat ARDS in mouse and pig models, suggests that this is not of a great concern ( Eliseeva et al, 2021 ). Some inflammatory responses can be potentially provoked by any unmethylated CpG motifs in plasmids, but this can be reduced by plasmid modification ( Krieg et al, 1995 ; Nishikawa and Huang, 2001 ).…”

Targeted Nanocarriers Co-Opting Pulmonary Intravascular Leukocytes for Drug Delivery to the Injured Brain

“…The intravascular leukocyte pool consists of those that are freely flowing in the bloodstream and those that are marginated within vascular beds. The pulmonary circulation hosts the largest and most dynamic pool of intravascular WBC that are poised to quickly respond to local and remote signals from damaged tissues. , The marginated pool of WBC consists of peripheral WBC that transiently dwell in the pulmonary circulation associated with the endothelial surface, constantly exchanging with the pool that is freely flowing in circulation . In fact, following acute inflammatory insults, WBC margination in the pulmonary capillaries is significantly enhanced, creating a “carpet” of WBC coating the endothelial cells lining the vessel wall. − Targeting to this pool of leukocytes has been shown to have therapeutic benefits in the treatment of acute lung injury; ,, however, it has not been explored to date for drug delivery for nonpulmonary conditions.…”

“…The pulmonary circulation hosts the largest and most dynamic pool of intravascular WBC that are poised to quickly respond to local and remote signals from damaged tissues. 45 , 46 The marginated pool of WBC consists of peripheral WBC that transiently dwell in the pulmonary circulation associated with the endothelial surface, constantly exchanging with the pool that is freely flowing in circulation. 37 In fact, following acute inflammatory insults, WBC margination in the pulmonary capillaries is significantly enhanced, creating a “carpet” of WBC coating the endothelial cells lining the vessel wall.…”