Zabel D D, Feng J J, Scheuenstuhl H, Hunt T K, Hussain M Z
Department of Surgery, University of California, San Francisco, USA.
Lab Invest. 1996 Mar;74(3):644-9.
Injury and inflammation lead to hypoxia and elevated lactate in wounds. This redox environment establishes cells in a reparative phenotype and leads macrophages to release angiogenic substances by unclear mechanisms. We investigated compounds known to modulate polyadenosine diphophoribose (pADP-R) levels in their effect on macrophage-derived angiogenic activity. Macrophages cultured from rabbit bone marrow were exposed to lactate, nicotinamide, and/or beta-nicotinamide adenine dinucleotide (NAD+). Supernatants were assayed for angiogenesis, and macrophages were analyzed for NAD+ content, poly(ADP-ribose) synthetase activity, and total (ADP-ribose)n synthesis. Lactate-, nicotinamide-, and lactate and nicotinamide-treated macrophages elicited significantly increased angiogenic activity compared with control or NAD+-treated cells. Lactate treatment decreased NAD+ content by 42 +/- 4% and (ADP-ribose)n synthesis by 37 +/- 5%. Nicotinamide reduced poly(ADP-ribose) synthetase activity and poly(ADP-ribose) synthesis. Thus, macrophage-derived angiogenic activity may be mediated by the redox environment involving NAD+ metabolites.
