Tumor angiogenesis factors reduce leukocyte adhesion in vivo

Leukocyte-endothelium interactions are diminished in tumors, It is reported here that, in a tumor-free in vivo model, angiogenic factors can down-regu late leukocyte adhesion to endothelium. Slow releasing pellets were loaded with either basic fibroblast growth factor (bFGF), vascular endothelial cel l growth factor (VEGF) or vehicle alone and were placed in the scrotum of m ice. After 3 days, a single intrascrotal injection of 1 mu g/kg IL-1 beta w as given 4 h before vessels of the cremaster muscle were investigated for l eukocyte rolling and adhesion by means of intravital microscopy, Exposure o f normal tissue to either bFGF or VEGF resulted in markedly decreased level s of cytokine-induced leukocyte adhesion. Suppression of leukocyte rolling was not observed. Instead a moderate enhancement of rolling by VEGF was fou nd. The observed differences could not be explained by differences in fluid dynamic parameters or systemic leukocyte counts. In conclusion, evidence i s presented that, in vivo, angiogenic factors significantly reduce leukocyt e adhesion, the final step preceding leukocyte infiltration. This observati on may explain why tumors escape from immune surveillance.