Macrophage-induced Angiogenesis Is Mediated by Tumour Necrosis Factor-Alpha

Nature. 1987 Oct 15-21;329(6140):630-2. doi: 10.1038/329630a0.

Abstract

Macrophages are important in the induction of new blood vessel growth during wound repair, inflammation and tumour growth. We show here that tumour necrosis factor-alpha (TNF-alpha), a secretory product of activated macrophages that is believed to mediate tumour cytotoxicity, is a potent inducer of new blood vessel growth (angiogenesis). In vivo, TNF-alpha induces capillary blood vessel formation in the rat cornea and the developing chick chorioallantoic membrane at very low doses. In vitro, TNF-alpha 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-alpha, suggesting immunological features are common to TNF-alpha and the protein responsible for macrophage-derived angiogenic activity. In inflammation and wound repair, TNF-alpha could augment repair by stimulating new blood vessel growth; in tumours, TNF-alpha might both stimulate tumour development by promoting vessel growth and participate in tumour destruction by direct cytotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cornea / blood supply
  • Fibroblast Growth Factors / pharmacology
  • Macrophages / physiology*
  • Microcirculation
  • Neovascularization, Pathologic*
  • Rats
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Tumor Necrosis Factor-alpha
  • Fibroblast Growth Factors