Effect and mechanism of lipopolysaccharides-induced myeloid-derived suppressor cells on airway inflammation in asthmatic mice

Abstract

To explore the effect and mechanism of lipopolysaccharides (LPS)-induced CD11b⁺Gr-1⁺ myeloid-derived suppressor cells (MDSCs) on airway inflammation in asthmatic mice. A total of 34 female BALB/c mice were selected. Among them, 4 mice received an intraperitoneal injection of LPS for inducing the accumulation of MDSCs. And the MDSCs were separated with CD11b immunomagnetic beads from spleen extract. Another 30 mice were randomly divided into normal control, asthmatic and cell treatment groups. The mice in the asthmatic and cell treatment groups were sensitized with ovalbumin by a combination of intraperitoneal injection and challenges to establish the murine asthmatic model. At Days 14 and 21 post-sensitization, the mice in cell treatment group received an intravenous injection of LPS-induced MDSCs. At 24 hours after the last allergen challenge, the number of inflammatory cells were counted and morphological identification of leucocytes in bronchoalveolar lavage fluid (BALF) was performed to analyze the degree of airway inflammation in conjunctions with pathological sections. The BALF and serum levels of interleukin-13 were measured by enzyme-linked immunosorbent assay (ELISA). The number of CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Tregs) in peripheral blood was measured by flow cytometry. The total number of cells, the percentage of neutrophils and eosinophils of BALF in the cell treatment group [(17.0 ± 8.3)×10⁴/ml, 11.1% ± 2.0%, 9.8% ± 2.9%] were significantly lower than those in the asthmatic group [(36.0 ± 15.9)×10⁴/ml, 20.8% ± 4.0%, 14.1% ± 4.2%] (P = 0.000, 0.000, 0.011). Compared to the asthmatic group, the BALF and serum levels of IL-13 were significantly lower [(34.7 ± 7.1) vs (105.0 ± 9.0) ng/L, (34.0 ± 4.7) vs (48.1 ± 6.1) ng/L] (both P = 0.000) and the number of CD4⁺CD25⁺Foxp3⁺ regulatory T cells increased in peripheral blood (8.0% ± 1.3% vs 5.1% ± 2.1%, P = 0.002) and airway inflammation was significantly relieved in the cell treatment group. LPS-induced MDSCs may improve airway inflammation through up-regulating Tregs in peripheral blood and suppressing Th2 effector function in asthmatic mice.