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

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.

The potential role of human osteoblasts for periprosthetic osteolysis following exposure to wear particles

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“…For example, pathological angiogenesis is related to higher vascularisation of inflammatory areas and tumours providing their blood supply. Furthermore, VEGF is an indicator of several inflammatory conditions and also responsible for the migration of monocytes and the proliferation of several types of fibroblasts (16)(17)(18).…”

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Relevant aspects of the influence of chosen growth factors on the activity of the female reproductive system

“…Ponadto biorąc udział w angiogenezie oraz przebudowie macierzy zewnątrzkomórkowej, stanowi dodatkowe ogniwo, które sprzyja zarówno rozwojowi, jak i utrzymaniu przewlekłych odczynów zapalnych. Wykazano, iż podczas ostrego i przewlekłego procesu zapalnego VEGF z udziałem swoistych receptorów oraz poprzez zwiększenie ekspresji cząsteczek adhezyjnych aktywizuje migracje leukocytów, w tym również neutrofili (66). Najnowsze badania zespołu Sağsőz (53) uwidoczniły zmiany czasowe w lokalizacji pro-i antyangiostycznych czynników w macicach suk podczas poszczególnych faz cyklu płciowego.…”