Suppressive effect of basic fibroblast growth factor on transendothelial emigration of CD4(+) T-lymphocyte.
The effect of basic fibroblast growth factor (b-FGF), one of the commonest angiogenic factors in various cancer types, on lymphocyte adhesion and transmigration across the endothelial cell monolayer was investigated using human umbilical vein-derived endothelial cells (HUVEC) and type I collagen gel. Forty-eight h exposure of HUVEC with 2 ng/ml b-FGF significantly decreased the basal adhesion of lymphocytes to endothelial cells. The decrease ratio is further enhanced by the addition of shear stress in this assay system. When HUVEC was stimulated for the last 24 h with optimal conditions of recombinant interleukin 1 beta, the percentages of transmigration as well as adhesion were also decreased significantly by the presence of b-FGF. The expression of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 was down-regulated by b-FGF exposure in both resting and activated conditions by recombinant interleukin 1 beta, supposedly the main reason for this phenomenon. The migrating cells across b-FGF-stimulated HUVEC contained a markedly lower percentage of CD4(+) T-cells than those across non-treated HUVEC, although the 4B4(+)/2H4(+) ratio in CD4(+) T-cell populations did not differ significantly. These facts suggest that the presence of b-FGF in the angiogenic area suppresses lymphocyte emigration, especially that of CD4(+) T-cells, and thus causes insufficient helper function in local immune response. This effect of b-FGF was possibly one of the critical mechanisms by which cancer cells escape from the host immune reactions in the angiogenic stage of tumor development.
Kitayama
J
J
First Department of Surgery, University of Tokyo, Japan.
Nagawa
H
H
Yasuhara
H
H
Tsuno
N
N
Kimura
W
W
Shibata
Y
Y
Muto
T
T
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000032:analysis; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000187:drug effects; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D014471:Umbilical Veins / Q000737:chemistry / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D018799:Intercellular Adhesion Molecule-1