The granulopoietic cytokine response and enhancement of granulopoiesis in mice during endotoxemia

Shock. 2005 Apr;23(4):344-52. doi: 10.1097/


In response to bacterial infection, the production of neutrophils by the bone marrow is accelerated. This study investigated the granulopoietic cytokine response and granulopoiesis during endotoxemia. Male Balb/c mice were intravenously challenged with lipopolysaccharide (LPS, 20 microg in 100 microL of saline per mouse). Control animals received saline alone. In a separate set of experiments, i.v. murine granulocyte colony-stimulating factor (G-CSF; 20 microg/kg) or vehicle (5% dextrose) was administered to mice. Endotoxemia caused a marked increase in G-CSF, keratinocyte-derived chemokine (KC), and macrophage inflammatory protein-2 (MIP-2) in the plasma and bone marrow between 1 and 4 h after the challenge. G-CSF, KC, and MIP-2 mRNA expression was also upregulated in the lung, liver, spleen, and bone marrow between 1 and 4 h after i.v. LPS. Intravenous administration of G-CSF caused a significant increase in G-CSF concentration in the plasma and bone marrow without upregulating G-CSF mRNA expression in the bone marrow. The levels of phospho-signal transducers and activators of transcription 3 and phospho-p44/42 mitogen-activated protein kinase were elevated in bone marrow cells at 30 min and 4 h after i.v. G-CSF and LPS, respectively. Granulocyte-macrophage colony-forming unit counts were significantly increased in the bone marrow, spleen, and blood at 48 h post-i.v. LPS or G-CSF. These data show that extramedullary organs produce granulopoietic cytokines in response to LPS. Because the tissue mass in extramedullary organs far exceeds that in the bone marrow, extramedullary production of these cytokines likely play a critical role in the regulation of the host's granulopoietic response to endotoxemia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Western
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism
  • Chemokine CXCL2
  • Chemokines / metabolism
  • Cytokines / metabolism*
  • DNA Primers / chemistry
  • DNA-Binding Proteins / metabolism
  • Endotoxemia*
  • Enzyme-Linked Immunosorbent Assay
  • Glucose / pharmacology
  • Granulocyte Colony-Stimulating Factor / metabolism
  • Granulocytes / cytology*
  • Granulocytes / metabolism*
  • Keratinocytes / metabolism
  • Lipopolysaccharides / metabolism*
  • Lipopolysaccharides / pharmacology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Phosphorylation
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor
  • Sodium Chloride / pharmacology
  • Time Factors
  • Trans-Activators / metabolism


  • Chemokine CXCL2
  • Chemokines
  • Cxcl2 protein, mouse
  • Cytokines
  • DNA Primers
  • DNA-Binding Proteins
  • Lipopolysaccharides
  • RNA, Messenger
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Trans-Activators
  • Granulocyte Colony-Stimulating Factor
  • Sodium Chloride
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Glucose