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. 2022 Feb 8;7(3):e149870. doi: 10.1172/jci.insight.149870

Figure 3. Genetic deletion and pharmacological inhibition of Adam8 protect mice against severe P. aeruginosa infection.

Figure 3

(A) Adam8–/– (white bars) or littermate controls (Adam8+/+, black bars) were intranasally instilled with P. aeruginosa (strain PA103) or vehicle control (PBS), then sacrificed 12 hours after infection. (B) Mouse Clinical Score for Sepsis (M-CASS) and (C) temperature scoring were determined in Adam8–/– (white) and Adam8+/+ (black) mice for P. aeruginosa–infected and control animals. (D) BAL neutrophils and (E) MPO levels. (F) WBCs and neutrophils in the peripheral blood of Adam8+/+ and Adam8–/– mice infected with P. aeruginosa (blue) or instilled with PBS (gray). (G) Representative histologic tissue sections of Adam8+/+ and Adam8–/– mice after 12 hours’ P. aeruginosa challenge. Arrowheads, neutrophils in the airspaces; scale bar, 50 μm. (See enlarged sections in Supplemental Figure 12.) (H) BAL TNF-α and (I) total protein. CFU in (J) BAL, (K) blood, and (L) spleen, respectively. (A and B) Box-and-whisker plots; (C–L) mean ± SD. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001, 2-way ANOVA followed by Holm-Šídák multiple-comparison test. (M) C57BL/6J mice were inoculated with P. aeruginosa and treated with either cyclic ADAM8 inhibitor peptide (BK-1361, dotted white bars) or control peptide (CP, dotted black bars) at 2 and 12 hours after infection, and sacrificed at 24 hours. (N) M-CASS and (O) temperature scoring. (P) BAL neutrophils and (Q) total protein. (R) Representative histologic tissue sections of mice treated with CP or BK-1361 during P. aeruginosa challenge. Arrowheads, neutrophils in the airspaces; scale bar, 50 μm. (See enlarged sections in Supplemental Figure 12.) CFU in (S) BAL, (T) blood, and (U) spleen. (N and O) Box-and-whisker plots; (Q–U) mean ± SD; individual data points for each animal are plotted as gray dots. * P < 0.05; ** P < 0.01; Student’s t test.