Figure 5. The selective β2-AR agonist bambuterol increases the generation of donor BM-derived myeloid-derived suppressor cells (MDSCs).

(A) CD11b⁺Gr-1⁺ (MDSC) frequencies within single live H-2^b+H-2^d–CD45⁺ populations from spleens and liver, 7 and 14 days after allo-HCT in the B6 → BALB/c model transplanted with 3.5 × 10⁶ WT C57BL/6 TCD-BM combined with 0.7 × 10⁶ WT C57BL/6 pan–T cells treated with daily saline and bambuterol injections. Data pooled from 2 individual experiments; total n = 5–6 per group. Bambuterol significantly increased MDSCs in spleen and liver compared with controls. (B) In vitro generation of BM MDSCs isolated from WT C57BL/6 mice in presence of terbutaline or terbutaline plus propranolol. Data pooled from 3 individual experiments, each with 2–3 replicates per group. Terbutaline significantly increased in vitro MDSC generation, which was blocked by propranolol. (C) In vitro generation of BM MDSCs isolated from WT or β2-AR^–/– C57BL/6 mice in presence of terbutaline. Data pooled from 3 individual experiments, each with 2–3 replicates per group. Terbutaline significantly increased in vitro MDSC generation from WT but not β2-AR^–/– BM. (D) Schematic design and MDSC generation from WT (CD45.1 H-2^b) and β2-AR^–/– (CD45.2 H-2^b) TCD-BM gated on single live H-2^d–CD3^– cells. Lethally irradiated BALB/c mice were transplanted with 3.5 × 10⁶ WT (CD45.1) and β2-AR^–/– (CD45.2) C57BL/6 TCD-BM (50:50 ratios) combined with 0.7 × 10⁶ WT (CD45.2) C57BL/6 pan–T cells. Recipients were treated with daily bambuterol injections. Data pooled from 2 individual experiments, each with n = 5 per group obtaining a total of n = 10 per group. At day 7 after allo-HCT, liver and spleen WT MDSC percentages were significantly higher compared with β2-AR^–/–. For comparison of the means, an unpaired 2-tailed t test was used in A and D, and a 1-way ANOVA with Bonferroni’s post hoc test was used in B and C. *P < 0.05, **P < 0.01, ***P < 0.001. Data are presented as median ± min to max.