Priming of monocyte for transendothelial migration by granulocyte-macrophage colony-stimulating factor: Requirement for chemoattractant and CD11/CD18 mechanisms

Monocyte transendothelial migration(TEM) into inflammed tissues involves adhesion molecules and chemotactic factors. However, cytokines and growth factors in inflammatory microeovironments might modulate the responses. Granulocyte-macrophage colony-stimulating factor(GM-CSF) enhances aad primes monocyte functions, but its role in monocyte TEM is poorly understood. In this study, using monocyte migration through a barrier of human umbilical vein endothelial cell(HUVEC) grown on microporous filters, we demonstrate that GM-CSF enhances monocyte TEM in response to C5a or MCP-1 through unstimulated HUVEC, increasing the migration from 28.7±5.3% (Mean±SEM) to 41.8±6.2% in the presence of GM-CSF(40ng/ml)(n=8, p<0.05). This effect was GM-CSF dose dependent. GM-CSF itself had no chemotactic or chemokinetic effect. GM-CSF also enhanced monocyte migration across IL-1 activated(5hr) HUVEC in the presence of a C5a chemotactic gradient, increasing the migration from 34.8±6% to 50.3±3.1% (n=3, p<0.05). The GM-CSF enhanced monocyte TEM was inhibited under both conditions by mAb to CD18 but not by mAb to VLA-4. The results indicate that: (a) GM-CSF can prime monocytes to the action of chemoattractant such aa C5a or MCP-1, thereby increasing monocyte TEM and, (b) the effect of GM-CSF was to enhance the CD11/CD18 adhesion molecule mechanism for TEM. Thus GM-CSF produced during inflammation may significantly upregulate monocyte TEM via CD11/CD18 mechanisms.