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Departments of Pediatrics, Microbiology and Immunology, and Pathology, Dalhousie University, Halifax, Nova Scotia, Canada
Correspondence: Dr. Andrew C. Issekutz, Department of Pediatrics, IWK Health Centre, 5850 University Ave., Halifax, Nova Scotia, Canada B3J 3G9. E-mail: Andrew.Issekutz{at}iwk.nshealth.ca
The effects of the angiogenic factors basic fibroblast growth factor
(bFGF) and vascular endothelial growth factor (VEGF) on human
polymorphonuclear leukocyte (PMNL)-endothelial cell adhesion and
transendothelial migration (TEM) were investigated. Stimulation of
human umbilical vein endothelial cells by VEGF or bFGF for 18 h
up-regulated intercellular adhesion molecule 1 and vascular cell
adhesion molecule 1 expression and significantly increased PMNL
adhesion and TEM in response to complement fragment 5a (C5a) or
interleukin (IL)-8. In contrast, continued exposure to bFGF (24 h–6
days) down-regulated basal and IL-1- or tumor necrosis factor
(TNF)-induced intercellular adhesion molecule 1, vascular cell adhesion
molecule 1, and E-selectin expression as well as PMNL adhesion and TEM.
These effects could be reversed by introduction of high concentrations
of TNF-
, C5a, or IL-8. None of these inhibitory effects was observed
with VEGF. The acute effects of bFGF and VEGF may facilitate PMNL
emigration during acute inflammation, but continued bFGF production may
have anti-inflammatory actions during chronic inflammation,
angiogenesis, and tumor defense by inhibition of endothelial activation
for leukocyte recruitment.
Key Words: bFGF • VEGF • leukocyte • endothelium • adhesion molecule
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