Macropinocytosis enhances foamy macrophage formation and cholesterol crystallization to activate NLRP3 inflammasome after spinal cord injury

After a spinal cord injury (SCI), the body's clean-up cells, called phagocytes, engulf myelin debris, forming foam cells that worsen inflammation. This study found that macrophages, a type of phagocyte, become foam cells by internalizing myelin debris through a process called macropinocytosis. This process leads to cholesterol crystals forming inside the macrophages, which triggers the activation of a protein complex called NLRP3 inflammasome. This activation increases the release of interleukin-1β (IL-1β), a molecule that promotes inflammation. Blocking macropinocytosis may lessen these effects, leading to better nerve regeneration, reduced nerve cell death, and improved outcomes after SCI. The study suggests that targeting macropinocytosis could be a promising treatment strategy for SCI.

• 1
  Foam cells formed after myelin debris internalization were predominantly macrophages rather than microglia after spinal cord injury.
• 2
  Receptor-independent macropinocytosis has an important position in foamy macrophage formation through engagement of myelin debris endocytosis after SCI.
• 3
  Inhibition of macropinocytosis might reverse this effect, resulting in enhanced axonal regeneration and reduced neural apoptosis, thereby improving outcomes after SCI.