Basic fibroblast growth factor (bFGF, FGF-2) potentiates leukocyte recruitment to inflammation by enhancing endothelial adhesion molecule expression.
Basic fibroblast growth factor (bFGF, FGF-2) is a potent angiogenic factor and endothelial cell mitogen. Although bFGF levels are increased in chronically inflamed tissue, its role in inflammation is unclear. We investigated the effect of bFGF on acute dermal inflammation and the recruitment of monocytes, T cells, and neutrophils. Leukocyte recruitment to inflamed sites was quantified with radiolabeled leukocytes. Intradermal injection of bFGF in rats did not induce leukocyte recruitment or inflammation. However, the recruitment of leukocytes to inflammation induced by tumor necrosis factor-alpha, interferon-gamma, C5a, or a delayed hypersensitivity reaction was enhanced by bFGF by 55 to 132% (P < 0.05). Either acute or prolonged bFGF treatment of dermal sites had this effect. The potentiating effect of bFGF on leukocyte recruitment was also seen in joints. There was no associated modulation of vascular permeability, blood flow, or angiogenesis in the sites by bFGF. However, the expression of the endothelial cell adhesion molecules (CAMs) for leukocytes, P-selectin, E-selectin, and ICAM-1, was significantly up-regulated in the inflamed tissue by bFGF, as quantified by radiolabeled anti-CAM antibody binding in vivo. Thus, although not directly proinflammatory, bFGF synergistically potentiates inflammatory mediator-induced leukocyte recruitment, at least in part, by enhancing CAM up-regulation on endothelium.
Zittermann
Sandra I
SI
Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
Issekutz
Andrew C
AC
D000818:Animals; D001808:Blood Vessels / Q000276:immunology / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003872:Dermatitis / Q000276:immunology* / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D036904:Leukocyte Rolling; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology*; D008297:Male; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D051381:Rats; D012867:Skin / Q000098:blood supply / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019007:P-Selectin; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma