Fig 2: The levels of serum S100A12 in different prognostic outcomes of CAP patients. (A–E) The level of serum S100A12 was detected via ELISA in CAP patients. (A) The level of serum S100A12 in CAP patients with or without mechanical ventilation. (B) The level of serum S100A12 in CAP patients with or without vasoactive agent. (C) The level of serum S100A12 in CAP patients with or without ICU admission. (D) The level of serum S100A12 in CAP patients with different hospital stays. (E) The level of serum S100A12 in alive and dead CAP patients. Data were expressed as mean ± SEM. * p < 0.05, ** p < 0.01.

Fig 3: S100A8/A9 and S100A12 played their pro-inflammatory effects through the p38 MAPK/NF-?B p65 pathway. The full-length blot of GAPDH in A was absent for the limited exposure space. A S100A8/A9 and S100A12 induced p38 MAPK phosphorylation and NF-?B p65 expression. B The phosphorylation ratios of p38 after neutrophils were stimulated with a combination of ANCA and S100A8/A9 or S100A12. C The activation of NF-?B p65 after neutrophils were stimulated with a combination of ANCA and S100A8/A9 or S100A12. D The phosphorylation of p38 MAPK and the activation of NF-?B p65 after the blockade of TLR4 and RAGE. E The phosphorylation ratio of p38 after blocking TLR4 and RAGE. F The expression of NF-?B p65 after blocking TLR4 and RAGE. *p < 0.05, **p < 0.01, ns: not significant

Fig 4: Effects of S100A8/A9 and S100A12 on the production of ROS and NETs in AAV. A–I Representative images of influences of S100A8/A9 and S100A12 on ANCA-induced production of ROS. Neutrophils were incubated with different stimulators and analyzed using flow cytometry. A Neutrophils were incubated with PBS. B Neutrophils were incubated with normal-IgG. C Neutrophils were incubated with ANCA. D–F Neutrophils were incubated with ANCA combined with 1, 5, and 10 µg/ml S100A8/A9, respectively. G–I Neutrophils were incubated with ANCA combined with 1, 5, and 10 µg/ml S100A12, respectively. J The mean fluorescence intensity of ROS after neutrophils were incubated with different stimulators. K Effects of S100A8/A9 and S100A12 on ANCA-induced formation of NETs. NE: neutrophil elastase

Fig 5: S100A8/A9 and S100A12 enhanced the release of IL-1ß and complement activation of ANCA-stimulated neutrophils through TLR4/RAGE. A Effects of S100A8/A9 and S100A12 on the release of IL-1ß from ANCA-activated neutrophils. B–D Effects of S100A8/A9 and S100A12 on the supernatant concentrations of C5a, CBb, and sC5b-9 of ANCA-activated neutrophils. *p < 0.05, **p < 0.01, ***p < 0.001, ns: not significant