Platelet-derived Wnt antagonist Dickkopf-1 is implicated in ICAM-1/VCAM-1-mediated neutrophilic acute lung inflammation.

Neutrophil infiltration represents the early acute inflammatory response in acute lung injury. The recruitment of neutrophils from the peripheral blood across the endothelial-epithelial barrier into the alveolar airspace is highly regulated by the adhesion molecules on alveolar epithelial cells (AECs). Wnt/ß-catenin signaling is involved in the progression of inflammatory lung diseases including asthma, emphysema, and pulmonary fibrosis. However, the function of Wnt/ß-catenin signaling in acute lung inflammation is unknown. Here, we identified platelet-derived Dickkopf-1 (Dkk1) as the major Wnt antagonist contributing to the suppression of Wnt/ß-catenin signaling in AECs during acute lung inflammation. Intratracheal administration of Wnt3a or an antibody capable of neutralizing Dkk1 inhibited neutrophil influx into the alveolar airspace of injured lungs. Activation of Wnt/ß-catenin signaling in AECs attenuated intercellular adhesion molecule 1 (ICAM-1)/vascular cell adhesion molecule 1 (VCAM-1)-mediated adhesion of both macrophages and neutrophils to AECs. Our results suggest a role for Wnt/ß-catenin signaling in modulating the inflammatory response, and a functional communication between platelets and AECs during acute lung inflammation. Targeting Wnt/ß-catenin signaling and the communication between platelets and AECs therefore represents potential therapeutic strategies to limit the damage of acute pulmonary inflammation.

Amygdala lesions in rhesus monkeys fail to disrupt object choices based on internal context.

We assessed the involvement of the amygdala in a task in which object choices were guided by internal context. Rhesus monkeys were trained on a biconditional discrimination whereby objects associated with food (but not water) were baited when the monkey was hungry, and objects associated with water (but not food) were baited when the monkey was thirsty. To solve this task, monkeys were required to choose objects yielding the reward congruent with their internal motivational state. Lesions of the amygdala did not disrupt learning or performance of this task. We conclude that the involvement of the amygdala in selective-satiation tasks, which depends in part on a change in internal context, is not due to the amygdala playing a general role in representing, or using, internal context.