G‐CSF induces leukocyte recruitment in vivo via the leukocyte G‐CSF receptor

Abstract

Granulocyte colony stimulating factor (G‐CSF) is in routine clinical use but has been shown to activate neutrophil adhesion in vitro. The aim of this study was to determine if G‐CSF is capable of inducing leukocyte‐endothelial cell interactions in vivo. Mice were treated with G‐CSF either by acute, local administration, or systemically over 4 hrs, and leukocyte‐endothelial cell interactions assessed via intravital microscopy of the cremasteric microcirculation. Local application of G‐CSF caused a reduction in leukocyte rolling but induced a significant increase in leukocyte adhesion within 15 mins, a process dependent on Mac‐1. The adherent cells were exclusively Gr‐1+ neutrophils. Adherent leukocytes also underwent transmigration within 45 mins. To assess the effect of G‐CSF under conditions mimicking its clinical use, G‐CSF was also administered systemically. Systemic G‐CSF induced increased leukocyte rolling, adhesion and transmigration after 4 hrs. Using mice rendered chimeric for the G‐CSF receptor (G‐CSFR) via bone marrow transfer between wild‐type and G‐CSFR−/− mice, this response was found to be dependent on leukocyte‐expressed G‐CSFR. These findings indicate a pro‐inflammatory role for G‐CSF and provide a potential mechanism for the association of G‐CSF administration with exacerbation of diseases such as rheumatoid arthritis.Supported by the NHMRC (Australia)