A key role for G-CSF-induced neutrophil production and trafficking during inflammatory arthritis

Blood. 2008 Dec 15;112(13):5193-201. doi: 10.1182/blood-2008-02-139535. Epub 2008 Sep 29.


We have previously shown that G-CSF-deficient (G-CSF(-/-)) mice are markedly protected from collagen-induced arthritis (CIA), which is the major murine model of rheumatoid arthritis, and now investigate the mechanisms by which G-CSF can promote inflammatory disease. Serum G-CSF levels were significantly elevated during CIA. Reciprocal bone marrow chimeras using G-CSF(-/-), G-CSFR(-/-), and wild-type (WT) mice identified nonhematopoietic cells as the major producers of G-CSF and hematopoietic cells as the major responders to G-CSF during CIA. Protection against CIA was associated with relative neutropenia. Depletion of neutrophils or blockade of the neutrophil adhesion molecule, Mac-1, dramatically attenuated the progression of established CIA in WT mice. Intravital microscopy of the microcirculation showed that both local and systemic administration of G-CSF significantly increased leukocyte trafficking into tissues in vivo. G-CSF-induced trafficking was Mac-1 dependent, and G-CSF up-regulated CD11b expression on neutrophils. Multiphoton microscopy of synovial vessels in the knee joint during CIA revealed significantly fewer adherent Gr-1(+) neutrophils in G-CSF(-/-) mice compared with WT mice. These data confirm a central proinflammatory role for G-CSF in the pathogenesis of inflammatory arthritis, which may be due to the promotion of neutrophil trafficking into inflamed joints, in addition to G-CSF-induced neutrophil production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / pathology*
  • Arthritis, Rheumatoid / pathology
  • CD11b Antigen
  • Chemotaxis, Leukocyte / drug effects
  • Granulocyte Colony-Stimulating Factor / blood
  • Granulocyte Colony-Stimulating Factor / genetics
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Knee Joint / pathology
  • Leukopoiesis / drug effects
  • Macrophage-1 Antigen
  • Mice
  • Mice, Knockout
  • Neutrophils / drug effects*
  • Synovial Fluid


  • CD11b Antigen
  • Macrophage-1 Antigen
  • Granulocyte Colony-Stimulating Factor