Selective inhibition of histone deacetylase 6 alters the composition of circulating blood cells in a lethal septic model

Ting Zhao, Yongqing Li, Baoling Liu, Ihab Halaweish, Ralph Mazitschek, Hasan B. Alam*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background Phagocytes, especially monocytes, macrophages, and dendritic cells, play a pivotal role in the innate and adaptive immune responses during sepsis. We have shown that inhibition of histone deacetylase 6 improves survival and increases bacterial clearance in a mouse model of cecal ligation and puncture (CLP). The aim of this study was to determine whether this effect was associated with changes in the number and composition of different blood cell types in the circulation. Methods C57BL/6J mice were subjected to CLP, and 1 h later given an intraperitoneal injection of either Tubastatin A dissolved in dimethyl sulfoxide, or dimethyl sulfoxide only. Sham-operated animals were treated in an identical fashion but not subjected to CLP. Forty-eight hours later, peripheral blood was obtained via cardiac puncture and analyzed using a HemaTrue veterinary hematology analyzer. Results Tubastatin A administration increased the number of circulating monocytes in the sham-operated and the CLP animals. In comparison with the sham, CLP animals displayed an increase in the granulocyte percentage in white blood cells and decrease in the lymphocyte number and percentage, with a resultant increase in the granulocyte-to- lymphocyte ratio. Treatment of CLP animals with Tubastatin A decreased the granulocyte percentage and restored the lymphocyte number and percentage, which decreased the granulocyte-to-lymphocyte ratio. In the sham animals, Tubastatin A increased red blood cell number, hematocrit, and hemoglobin. This effect was not seen in CLP animals. Conclusions Tubastatin A treatment has significant impact on the composition of circulating blood cells. It increases the number of circulating monocytes and the red blood cell mass in sham-operated animals. In the CLP animals, it increases the monocyte count, decreases the percentage of granulocytes, restores the lymphocyte population, and decreases the granulocyte-to-lymphocyte ratio. These results may explain why Tubastatin A treatment improves survival in the septic models.

Original languageEnglish (US)
Pages (from-to)647-654
Number of pages8
JournalJournal of Surgical Research
Volume190
Issue number2
DOIs
StatePublished - Aug 2014
Externally publishedYes

Keywords

  • Blood
  • Granulocyte
  • Histone deacetylase 6
  • Lymphocyte
  • Sepsis
  • Tubastatin A

ASJC Scopus subject areas

  • Surgery

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