Lactate stimulation of macrophage-derived angiogenic activity is associated with inhibition of Poly(ADP-ribose) synthesis.
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.
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Department of Surgery, University of California, San Francisco, USA.
Feng
J J
JJ
Scheuenstuhl
H
H
Hunt
T K
TK
Hussain
M Z
MZ
D000818:Animals; D002478:Cells, Cultured; D003315:Cornea / Q000098:blood supply / Q000187:drug effects; D007773:Lactates / Q000494:pharmacology*; D019344:Lactic Acid; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology*; D009243:NAD / Q000378:metabolism / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology*; D009536:Niacinamide / Q000494:pharmacology; D010084:Oxidation-Reduction; D011064:Poly Adenosine Diphosphate Ribose / Q000096:biosynthesis*; D011817:Rabbits
D007773:Lactates; D009243:NAD; D009536:Niacinamide; D011064:Poly Adenosine Diphosphate Ribose; D019344:Lactic Acid