Accuri C6 Flow Cytometer System
Originally published online as doi:10.1189/jlb.1205718 on July 3, 2006

Published online before print July 3, 2006
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(Journal of Leukocyte Biology. 2006;80:247-257.)
© 2006 by Society for Leukocyte Biology

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

Sandra I. Zittermann* and Andrew C. Issekutz*,{dagger},{ddagger},1

* Departments of Pediatrics,
{dagger} Pathology, and
{ddagger} Microbiology-Immunology, Dalhousie University, Halifax, Nova Scotia, Canada

1Correspondence: Dalhousie University, Department of Pediatrics, Room 8504, 8 East Research Labs, IWK Health Centre, 5850/5980 University Avenue, Halifax, NS, Canada B3K 6R8. E-mail: Andrew.Issekutz{at}iwk.nshealth.ca

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 {alpha} (TNF-{alpha})-induced monocyte recruitment by 39 ± 16% and increased P-selectin, E-selectin, and intercellular CAM-1 expression by two- to threefold over TNF-{alpha} alone. However, recruitment of monocytes to TNF-{alpha} + interferon-{gamma} (IFN-{gamma}) 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-{alpha} + IFN-{gamma} 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-{alpha} + IFN-{gamma}-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.

Key Words: adhesion molecule • chemokine • inflammatory mediator


Related Article

Interview with Dr. Andrew Issekutz regarding Pivotal Advance: Endothelial growth factors VEGF and bFGF differentially modulate monocyte and neutrophil recruitment to inflammation
Helene F. Rosenberg
J. Leukoc. Biol. 2006 80: 245-246. [Full Text] [PDF]



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