In the cycle of fibrosis, which stage follows macrophage infiltration and activation?

• A. Increased collagen synthesis
• B. Myofibroblast infiltration and activation
• C. Vascular support system increased
• D. Connective tissue shrinkage

Answer: (C)

Macrophage-driven signaling pushes repair toward fibrogenesis by activating fibroblasts into myofibroblasts. When macrophages infiltrate and become activated, they release cytokines such as TGF-β that recruit fibroblasts to the injury site and drive their differentiation into myofibroblasts. These myofibroblasts are the cells responsible for the next phase: producing large amounts of collagen and other extracellular matrix components, remodeling the tissue, and contracting the wound. So the stage that follows macrophage infiltration and activation is myofibroblast infiltration and activation, which then leads to increased collagen synthesis and matrix remodeling. While the vascular network does expand during healing, the immediate fibrogenic step right after macrophage activation is the activation of myofibroblasts.