Endothelial growth factors VEGF and bFGF differentially enhance monocyte and neutrophil recruitment to inflammation

Publisher Website
Google Scholar
Abstract
Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are produced at sites of inflammation. Previously, we demonstrated that bFGF enhances leukocyte recruitment and endothelial cell adhesion molecule (CAM) expression during inflammation. Here, we investigated the influence of VEGF during acute inflammation and whether VEGF and bFGF cooperate to modulate leukocyte recruitment. Inflammation was induced in skin of rats by intradermal injection of inflammatory stimuli ± VEGF ± bFGF. Migration of 51Cr-monocytes and 111In-polymorphonuclear leukocytes (PMN) to the dermal lesions and 125I-anti-CAM monoclonal antibody binding to the dermal vasculature were quantitated after 2 h. VEGF significantly enhanced tumor necrosis factor α (TNF-α)-induced monocyte recruitment by 39 ± 16% and increased P-selectin, E-selectin, and intercellular CAM-1 expression by two- to threefold over TNF-α alone. However, recruitment of monocytes to TNF-α + interferon-γ (IFN-γ) and of PMN to all stimuli tested was not affected by VEGF. In contrast, bFGF enhanced recruitment of both leukocyte types to all stimuli tested. With the potent TNF-α + IFN-γ stimulus, in contrast to bFGF, VEGF did not enhance E-selectin or ICAM-1 expression. bFGF, but not VEGF, increased the chemotactic activity for PMN in TNF-α + IFN-γ-inflamed sites by 54%. The limited effect of VEGF on these mechanisms likely contributed to the differential effect of VEGF and bFGF on leukocyte recruitment. However, VEGF + bFGF increased PMN recruitment more than did either factor alone. Thus, bFGF and VEGF differentially but synergistically enhance leukocyte recruitment to inflammatory stimuli and individually as well as jointly function as positive regulators of inflammatory cell recruitment.
Funding Information
  • Canadian Institutes of Health Research (MT-7684, MGC-57081)

This publication has 46 references indexed in Scilit: