Shear Stress Induces a Time-Dependent Inflammatory Response in Human Monocyte-Derived Macrophages

Abstract

Macrophages are innate immune cells that are known for their diverse phenotypes and plasticity. They switch between pro-inflammatory and anti-inflammatory/pro-fibrotic phenotypes depending on surrounding microenvironmental cues. Although much research has been focused on their response to biochemical cues and mechanical signals, there is a paucity of knowledge surrounding macrophage behavior in response to shear stress even though shear stress has been implicated to affect macrophage phenotype in diseases such as atherosclerosis. It is also difficult to determine the specific signals that macrophages release in response to shear in vivo, necessitating a more controlled environment using an in vitro model. We achieved this by applying varying magnitudes of shear stress on monocyte-derived macrophages (MDMs) using a cone-and-plate viscometer and evaluated changes in genetic expression, protein expression, and cytokine secretion. Interestingly, we found that prolonged shear exposure induced a pro-inflammatory M1 phenotype. These findings have implications in applications such as in situ vascular graft design, where macrophages are exposed to shear and have been shown to affect graft resorption. Future studies should evaluate longer timepoints and higher shear rates.

Computational Insights into Colonic Motility: Mechanical Role of Mucus in Homeostasis and Inflammation

“…Furthermore, shear stress is a key regulator of endothelial cell apoptosis (68). Several studies have also reported that high shear stress may promote the activation of immune cells, including T cells, neutrophils, and macrophages (15,16,69) and pro-inflammatory cytokine secretion (70). Therefore, this observation suggests that shear stress may have an important role in the cell-shedding process.…”

“…In advanced cell models such as organoids and induced pluripotent stem cells (iPSCs) and their combinations with organ-on-a-chip (OoC), the mucus layer is either missing as a layer and shown as a protein expression in the models or fail to form a distinct mucosal layer. Consequently, although the importance of shear stress has been repeatedly shown in OoC models, no general framework exists to account for the interplay of shear stress, epithelial barrier, and intestinal mucus (10)(11)(12)(13)(14)(15)(16)(17)(18).…”