Modulation of the Bcl-2 family blocks sepsis-induced depletion of dendritic cells and macrophages

Octavia M. Peck-Palmer, Jacqueline Unsinger, Katherine C. Chang, Jacquelyn S. McDonough, Harris Perlman, Jonathan E. McDunn, Richard S. Hotchkiss

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39 Scopus citations

Abstract

This study examined the fate of dendritic cells (DCs) and macrophages (MΦ) in vivo in a murine model of sepsis. Wild-type, knockout, and transgenic mice were used to examine the role of Bcl-2 family members on the regulation of splenic DCs and MPhi; survival. Bim knockout (Bim -/-) mice and mice overexpressing Bcl-2 in selected hematopoietic cells were used: (a) overexpression of Bcl-2 in all hematopoietic cells using a vav promoter (Vav-Bcl-2) and (b) overexpression of Bcl-2 in all Major histocompatibility complex (MHC) class I cells (H-2K-Bcl-2). Mice underwent sham surgery or cecal ligation and puncture, and absolute numbers of splenic DCs and MO were determined. Importantly, two distinct MPhi; populations, that is, well-differentiated "mature" MPhi; population and a less differentiated "immature," "monocyte-like" (IMPhi;) population were identified that demonstrated differential susceptibility to apoptosis. In wild-type mice, sepsis induced a 64% ± 7% and a 77% ± 3% decrease in absolute cell numbers of splenic DCs and IMPhi;, respectively (n = 7, P< 0.05). Mature MO were not depleted in sepsis. No significant cell depletion was evident in Vav-Bcl- 2, H-2K-Bcl-2, or Bim -/- mice. We conclude that sepsis induces a major depletion of developing MO as well as DCs, and this depletion may be an important mechanism of immune suppression in sepsis.

Original languageEnglish
Pages (from-to)359-366
Number of pages8
JournalShock
Volume31
Issue number4
DOIs
StatePublished - Apr 1 2009

Keywords

  • Apoptosis
  • Cecal ligation and puncture
  • Cytokine

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    Peck-Palmer, O. M., Unsinger, J., Chang, K. C., McDonough, J. S., Perlman, H., McDunn, J. E., & Hotchkiss, R. S. (2009). Modulation of the Bcl-2 family blocks sepsis-induced depletion of dendritic cells and macrophages. Shock, 31(4), 359-366. https://doi.org/10.1097/SHK.0b013e31818ba2a2