Figure 6. Proposed protective mechanisms of NET stabilization.

Left: NETs are subjected to digestion by DNase I, reducing microbial capture and liberating toxic NDPs, including cfDNA. These cfDNA fragments expose ssDNA at termini that trigger coagulation activation and induce endothelial injury, leading to thrombosis and end-organ dysfunction in sepsis. Right: NET stabilization by hPF4 enhances DNase I resistance, which enhances NET microbial capture, reduces circulating cfDNA levels, and attenuates cfDNA-induced thrombogenicity and toxicity to endothelial cells.