Regulation of steady-state neutrophil homeostasis by macrophages.

Published

Journal Article

The timely clearance of apoptotic neutrophils from inflammation sites is an important function of macrophages; however, the role of macrophages in maintaining neutrophil homeostasis under steady-state conditions is less well understood. By conditionally deleting the antiapoptotic gene cellular FLICE-like inhibitory protein (C-FLIP) in myeloid cells, we have generated a novel mouse model deficient in marginal zone and bone marrow stromal macrophages. These mice develop severe neutrophilia, splenomegaly, extramedullary hematopoiesis, decreased body weight, and increased production of granulocyte colony-stimulating factor (G-CSF) and IL-1β, but not IL-17. c-FLIP(f/f) LysM-Cre mice exhibit delayed clearance of circulating neutrophils, suggesting that failure of macrophages to efficiently clear apoptotic neutrophils causes production of cytokines that drive excess granulopoiesis. Further, blocking G-CSF but not IL-1R signaling in vivo rescues this neutrophilia, suggesting that a G-CSF-dependent, IL-1β-independent pathway plays a role in promoting neutrophil production in mice with defective clearance of apoptotic cells.

Full Text

Duke Authors

Cited Authors

  • Gordy, C; Pua, H; Sempowski, GD; He, Y-W

Published Date

  • January 13, 2011

Published In

Volume / Issue

  • 117 / 2

Start / End Page

  • 618 - 629

PubMed ID

  • 20980680

Pubmed Central ID

  • 20980680

Electronic International Standard Serial Number (EISSN)

  • 1528-0020

Digital Object Identifier (DOI)

  • 10.1182/blood-2010-01-265959

Language

  • eng

Conference Location

  • United States