Portal de Periódicos da CAPES

MODULATION OF THE BCL-2 FAMILY BLOCKS SEPSIS-INDUCED DEPLETION OF DENDRITIC CELLS AND MACROPHAGES

2009; Lippincott Williams & Wilkins; Volume: 31; Issue: 4 Linguagem: Inglês

10.1097/shk.0b013e31818ba2a2

1540-0514

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

Immunotherapy and Immune Responses

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 MΦ 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 MΦ were determined. Importantly, two distinct MΦ populations, that is, well-differentiated "mature" MΦ population and a less differentiated "immature," "monocyte-like" (IMΦ) 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 IMΦ, respectively (n = 7, P < 0.05). Mature MΦ 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 MΦ as well as DCs, and this depletion may be an important mechanism of immune suppression in sepsis.