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

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.

A novel role for TNFAIP2: its correlation with invasion and metastasis in nasopharyngeal carcinoma

“…TNFa has been shown to promote vascularization in rabbit cornea and chick chorioallantoic membrane, 33,34 and to induce the expression of various angiogenic factors, including VEGF. [35][36][37] Furthermore, VEGF expression was found to be markedly increased and correlated with microvessel density in nasopharyngeal carcinoma patients.…”

Inhibition of interleukin‐1 but not tumor necrosis factor suppresses neovascularization in rat models of corneal angiogenesis and adjuvant arthritis

“…tory cytokines in RA. Both IL-1 (13)(14)(15) and TNF␣ (16,17), 2 master cytokines that play a significant role in RA (3), are known to promote angiogenesis. Given this intense interest in anticytokine biologics, our experiments provide important new information regarding the ability of such novel therapeutic molecules to regulate neovascularization in the arthritic joint.…”

“…IL-1 (13)(14)(15) and TNF␣ (16)(17)(18)(19) both also have been implicated as angiogenic factors. This finding is provocative because angiogenesis is a critical component in the initiation and maintenance of pannus, the aggressive fibrovascular extension of synovial tissue that is responsible for the extensive bone and cartilage damage in RA (20) and experimental models of arthritis (21).…”

Effect of Octreotide on experimental corneal neovascularization

“…During pathologic conditions neovascularization and inflammatory reactions cause loss of transparency (Granzyna et al 1993). Inflammation results in elongation of stromal lamella and causes the release of angiogenic factors,prostaglandins and interleukins which activate neovascularization (Richard et al 1994;Leibovitch et al 1987). It is well known that multiple angiogenic factors take part in neovascularization.…”