Figure 5.

Neutrophil proteases involved in wound healing and their inhibitors. Neutrophils produce two main classes of proteases relevant to tissue repair. Serine proteases like elastase and cathepsin G target a variety of extracellular matrix proteins, including elastin, fibronectin, laminin, vitronectin, and collagen IV. The action of serine proteases is balanced by several protease inhibitors produced by neutrophils (α1-AT, SLPI) and surrounding skin cells (α1-ACT, SLPI, α2-M). Neutrophils also produce several types of MMPs. MMP-8, which cleaves fibrillar collagen, and MMP-2/MMP-9, which cleave collagen IV (among other substrates), are involved in wound repair. The activity of MMPs is inhibited by a class of molecules called TIMPs produced by a variety of cells in the skin. If the activity of proteases and their inhibitors is not tightly regulated, the protease activity can become extreme and impair the healing process.