Microphysiological Models of Lung Epithelium-Alveolar Macrophage Co-Cultures to Study Chronic Lung Disease.

The interactions between immune cells and epithelial cells influence the progression of many respiratory diseases, such as chronic obstructive pulmonary disease (COPD). In vitro models allow for the examination of cells in controlled environments. However, these models lack the complex 3D architecture and vast multicellular interactions between the lung resident cells and infiltrating immune cells that can mediate cellular response to insults. In this study, three complementary microphysiological systems are presented to delineate the effects of cigarette smoke and respiratory disease on the lung epithelium. First, the Transwell system allows the co-culture of pulmonary immune and epithelial cells to evaluate cellular and monolayer phenotypic changes in response to cigarette smoke exposure. Next, the human and mouse precision-cut lung slices system provides a physiologically relevant model to study the effects of chronic insults like cigarette smoke with the dissection of specific interaction of immune cell subtypes within the structurally complex tissue environment. Finally, the lung-on-a-chip model provides an adaptable system for live imaging of polarized epithelial tissues that mimic the in vivo environment of the airways. Using a combination of these models, a complementary approach is provided to better address the intricate mechanisms of lung disease.

Rat behavior and dopamine release are modulated by conspecific distress.

Rats exhibit 'empathy' making them a model to understand the neural underpinnings of such behavior. We show data consistent with these findings, but also that behavior and dopamine (DA) release reflects subjective rather than objective evaluation of appetitive and aversive events that occur to another. We recorded DA release in two paradigms: one that involved cues predictive of unavoidable shock to the conspecific and another that allowed the rat to refrain from reward when there were harmful consequences to the conspecific. Behavior and DA reflected pro-social interactions in that DA suppression was reduced during cues that predicted shock in the presence of the conspecific and that DA release observed on self-avoidance trials was present when the conspecific was spared. However, DA also increased when the conspecific was shocked instead of the recording rat and DA release during conspecific avoidance trials was lower than when the rat avoided shock for itself.