Inhibition of histone deacetylase 6 restores innate immune cells in the bone marrow in a lethal septic model.

摘要: BACKGROUND We have previously demonstrated that Tubastatin A, a selective inhibitor of histone deacetylase 6 (HDAC6), improves survival and increases circulating monocyte count bacterial clearance in lethal model cecal ligation puncture (CLP) mice. The aim the present study was to characterize effects inhibition HDAC6 on bone marrow cell population. METHODS C57BL/6J mice were subjected CLP and, 1 hour later, given an intraperitoneal injection either A (70 mg/kg) dissolved DMSO or alone (n = 9 per group). Sham-operated animals treated identical fashion, without CLP. Forty-eight hours cells flushed out from femurs tibias. Erythrocytes lysed, single-cell suspension made for analysis. Cells washed; blocked with antimouse CD16/32; stained B220 PE-Cy7, CD3 APC-eFluor 780, CD11b FITC, Gr-1 PerCP-Cy5.5, F4/80 Antigen APC; flow cytometry. Data acquired LSRII Flow Cytometer (BD Biosciences, San Jose, CA) analyzed FlowJo (Flowjo, LLC, Ashland, OR). RESULTS In comparison sham group, showed decreased percentage innate immune (CD11b, 62.1% ± 3.1% vs. 32.9% 4.9%, p 0.0025) macrophages (CD11bF4/80, 44.6% 3.4% 19.8% 2.6%, 0.0002) as well increased T lymphocytes (CD3, 1.1% 0.2% 3.3% 0.4%, 0.0082) 48 after Treatment restored (32.9% 4.9% 54.0% 4.1%, 0.0112) (19.8% 2.6% 47.1% 4.6%, 0.0001) neutrophils (CD11bGr-1, 28.4% 3.9% 48.0% 4.0%, 0.0075). percentages B (B220) not significantly altered by compared vehicle-treated animals. CONCLUSION Selective this septic macrophage populations neutrophil composition marrow. These results may explain reported beneficial treatment model.