Stress hormone signaling through β-adrenergic receptors regulates macrophage mechanotype and function

Critical functions of immune cells require them to rapidly change their shape and generate forces in response to cues from their surrounding environment. However, little is known about how soluble factors that may be present in the microenvironment modulate key aspects of cellular mechanobiology—such as immune cell deformability and force generation—to impact functions such as phagocytosis and migration. Here we show that signaling by soluble stress hormones through β-adrenoceptors (β-AR) reduces the deformability of macrophages; this is dependent on changes in the organization of the actin cytoskeleton and is associated with functional changes in phagocytosis and migration. Pharmacologic interventions reveal that the impact of β-AR signaling on macrophage deformability is dependent on actin-related proteins 2/3, indicating that stress hormone signaling through β-AR shifts actin organization to favor branched structures rather than linear unbranched actin filaments. These findings show that through remode...