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-regulate leukocyte adhesion to endothelium. Slow releasing pellets were loaded with either basic fibroblast growth factor (bFGF), vascular endothelial cell growth factor (VEGF) or vehicle alone and were placed in the scrotum of mice. After 3 days, a single intrascrotal injection of 1 microg/kg IL-1beta was given 4 h before vessels of the cremaster muscle were investigated for leukocyte rolling and adhesion by means of intravital microscopy. Exposure of normal tissue to either bFGF or VEGF resulted in markedly decreased levels of cytokine-induced leukocyte adhesion. Suppression of leukocyte rolling was not observed. Instead a moderate enhancement of rolling by VEGF was found. The observed differences could not be explained by differences in fluid dynamic parameters or systemic leukocyte counts. In conclusion, evidence is presented that, in vivo, angiogenic factors significantly reduce leukocyte adhesion, the final step preceding leukocyte infiltration. This observation may explain why tumors escape from immune surveillance.
Tromp
S C
SC
Departments of Physiology and Biophysics, Cardiovascular Research Institute Maastricht, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
oude Egbrink
M G
MG
Dings
R P
RP
van Velzen
S
S
Slaaf
D W
DW
Hillen
H F
HF
Tangelder
G J
GJ
Reneman
R S
RS
Griffioen
A W
AW
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004730:Endothelium, Vascular; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007375:Interleukin-1 / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology; D008222:Lymphokines / Q000494:pharmacology; D008297:Male; D051379:Mice; D012611:Scrotum / Q000098:blood supply; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D043925:Angiogenesis Inducing Agents; D016228:Endothelial Growth Factors; D007375:Interleukin-1; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D018799:Intercellular Adhesion Molecule-1