Michael Adducts of Palmitoylascorbic Acid: Effects on the Oxidative Burst of Neutrophils and the Production of Tumor Necrosis Factor-Alpha in Monocytes

Abstract

The effects of Michael adducts of 6-O-palmitoyl-L-ascorbic acid (compounds 1–4) on the phosphorylation-dependent response of stimulated monocytes and neutrophils was investigated. The pyranosyl derivative 3 increased the production of tumor necrosis factor-α in human monocytes stimulated with lipopolysaccharide (LPS). Compound 3 also enhanced the release of tumor necrosis factor-α from nonstimulated monocytes. Michael adducts 1–4 inhibited the formation of reactive oxygen species in fMLP-stimulated human neutrophils as measured by luminol chemiluminescence. Treatment with 6-O-palmitoyl-L-ascorbic acid (compound 5) also led to a decreased luminescence response of neutrophils. Results are discussed with respect to the inhibitory activity of Michael adducts of ascorbic acids towards protein phosphatases PP1/PP2A.