Enhancement of monocyte transendothelial migration by granulocyte-macrophage colony-stimulating factor: requirement for chemoattractant and CD11a/CD18 mechanisms

Granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances and prim es monocyte functions, but its role in monocyte migration is poorly underst ood. We examined monocyte migration across human umbilical vein endothelial cells (HUVEC) grown on filters. GMCSF had no chemotactic or chemokinetic e ffect. However, GM-CSF enhanced monocyte transendothelial migration (TEM) t hrough unstimulated and IL-1-activated (5 h) HUVEC in response to C5a or mo nocyte chemoattractant protein-1 in a dose-dependent fashion, increasing th e migration from 28.7 +/- 5.3% to 41.8 +/- 6.2% (n = 8, p < 0.05) and from 34.8 +/- 6% to 50.3 +/- 3.1%, p < 0.05), respectively. The enhanced TEM was inhibited by monoclonal antibodies (mAb) to LFA-1, but not by mAb to Mac-1 or to VLA-4. Furthermore, GM-CSF up-regulated and activated LFA-1, as asse ssed by NKI-L16 neoepitope expression. The results indicate that: (1) GM-CS F can prime monocytes for increased TEM, (2) GM-CSF enhances LFA-1-mediated monocyte TEM and (3) this effect is in part mediated by increasing LFA-1 e xpression and activation. Thus, increased GM-CSF production may promote mon ocyte accumulation in inflammation not only by inducing monocytosis, but al so enhancing migration.