Macrophage-induced angiogenesis is mediated by tumour necrosis factor-α

SJ Leibovich, PJ Polverini, HM Shepard, DM Wiseman… - Nature, 1987 - nature.com
SJ Leibovich, PJ Polverini, HM Shepard, DM Wiseman, V Shively, N Nuseir
Nature, 1987nature.com
Macrophages are important in the induction of new blood vessel growth during wound
repair, inflammation and tumour growth1–4. We show here that tumour necrosis factor-α
(TNF-α), a secretory product of activated macrophages that is believed to mediate tumour
cytotoxicity5–9, is a potent inducer of new blood vessel growth (angiogenesis). In vivo, TNF-
α induces capillary blood vessel formation in the rat cornea and the developing chick
chorioallantoic membrane at very low doses. In vitro, TNF-α stimulates chemotaxis of bovine …
Abstract
Macrophages are important in the induction of new blood vessel growth during wound repair, inflammation and tumour growth1–4. We show here that tumour necrosis factor-α (TNF-α), a secretory product of activated macrophages that is believed to mediate tumour cytotoxicity5–9, is a potent inducer of new blood vessel growth (angiogenesis). In vivo, TNF-α induces capillary blood vessel formation in the rat cornea and the developing chick chorioallantoic membrane at very low doses. In vitro, TNF-α stimulates chemotaxis of bovine adrenal capillary endothelial cells and induces cultures of these cells grown on type-1 collagen gels to form capillary-tube-like structures. The angiogenic activity produced by activated murine peritoneal macrophages is completely neutralized by a polyclonal antibody to TNF-α, suggesting immunological features are common to TNF-α and the protein responsible for macrophage-derived angiogenic activity. In inflammation and wound repair, TNF-α could augment repair by stimulating new blood vessel growth; in tumours, TNF-α might both stimulate tumour development by promoting vessel growth and participate in tumour destruction by direct cytotoxicity10–12.
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