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

Area of Science:

• Immunology
• Cell Biology
• Biophysics

Background:

• Macrophages exhibit plasticity, shifting between pro-inflammatory (M1) and anti-inflammatory (M2) states based on microenvironmental cues.
• While biochemical and mechanical signals are studied, macrophage response to shear stress remains under-explored.
• Shear stress is a critical factor in cardiovascular health and disease, influencing cellular behavior within blood vessels.

Purpose of the Study:

• To investigate the impact of varying shear stress magnitudes on human monocyte-derived macrophages (MDMs).
• To evaluate changes in MDM morphology, gene expression, protein expression, and cytokine secretion under shear stress.
• To determine if shear stress induces a pro-inflammatory or anti-inflammatory phenotype in MDMs.

Main Methods:

• Human monocyte-derived macrophages (MDMs) were subjected to controlled shear stress using a cone-and-plate viscometer.
• Morphological changes were assessed via microscopy.
• Gene expression was analyzed using RT-qPCR.
• Cytokine and chemokine secretion was measured over time.

Main Results:

• MDMs exposed to shear stress displayed a rounder morphology compared to static controls.
• Significant upregulation of Tumor Necrosis Factor-alpha (TNF-α) was observed.
• Increased secretion of Interleukin-8 (IL-8), Interleukin-18 (IL-18), and fractalkine was detected.
• Pro-inflammatory factor upregulation intensified with increasing shear stress magnitude and duration.

Conclusions:

• Prolonged shear stress exposure induces a pro-inflammatory phenotype in human MDMs.
• These findings are relevant for developing medical technologies like vascular grafts, where macrophages interact with shear stress.
• Understanding shear stress-induced macrophage responses can elucidate disease pathophysiology, such as in atherosclerosis.