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. Author manuscript; available in PMC: 2024 Jul 25.
Published in final edited form as: Sci Transl Med. 2024 Jul 3;16(754):eadi6887. doi: 10.1126/scitranslmed.adi6887

Figure 6: PI3Kγ inhibition suppresses inflammation and promotes survival in mouse models of acute respiratory distress syndrome and sepsis.

Figure 6:

(A) Kaplan-Meier survival plots of WT (n=8) and Pik3cg−/− mice (n=8) inoculated with methicillin-resistant Staphylococcus aureus (MRSA). B) Left, graph of mean ± SEM macrophages in thioglycolate-stimulated peritoneal exudates of WT and Pik3cg−/− (n=4) and in vehicle vs IPI-549 treated mice (n=4). Right, flow cytometry profiles of F4/80+ macrophages in peritoneal exudates from WT and Pik3cg−/− animals with and without thioglycolate treatment. (C) Schematic of animal models of acute respiratory distress syndrome and outcome measures. (D) Kaplan-Meier survival plots of female and male WT (n=10) and Pik3cg−/− (n=10) mice treated once with 10 mg/kg (acute) LPS. (E) Representative images of Giemsa-stained cells in BAL from WT or Pik3cg−/− animals stimulated with 12 mg/kg (acute) LPS or with 3 mg/kg (chronic) LPS or poly I:C and treated with vehicle or IPI-549. Arrowheads indicate macrophages. (F) Graph of macrophages/ml (mean ± SEM) in BAL from WT (n=5) versus Pik3cg−/− (n=5) and vehicle (n=5) versus IPI-549-treated (n=5) animals after treatment with acute LPS, chronic LPS or chronic poly I:C (G) H&E and anti-F4/80-stained images of lungs isolated from WT versus Pik3cg−/− and vehicle versus IPI-549-treated animals 96h after stimulation with chronic LPS. Arrowheads indicate macrophages. (H) Violin plots of macrophages/mm2 (mean and interquartile range indicated by dotted lines) in lungs from WT (n=5) versus Pik3cg−/− (n=5) and vehicle (n=5) versus IPI-549-treated (n=5) animals. (I) Schematic depicting vascular leak assay. (J) Graph of Evans blue concentration (mean μg/ml ± SEM) in lungs of naïve mice (n=7) or mice treated with chronic LPS (n=5), Poly I:C (n=5), or acute LPS (n=9–10) and vehicle or IPI-549-treatment. (K) Graph of mean ± SEM pg/ml TNF-α in serum from naïve (n=5) and chronic LPS-stimulated, vehicle- (n=5) or IPI-549-treated (n=5) animals. (L) Graph of cytokine mRNA expression (mean 2−ΔCT ± SEM) in CD11b+ cells from lungs of chronic LPS-stimulated animals treated with vehicle or IPI-549 (n=3). Statistical significance was determined by Log-rank Mantel-Cox test (A, D), one-way ANOVA with Tukey’s multiple comparisons test (J, K) or t test (B, F, H, L).