Carotenoid cleavage products modify respiratory burst and induce apoptosis of human neutrophils

Abstract

Carotenoid supplementation in the treatment of diseases associated with oxidative stress has been recently questioned because of the cell damage and the increased risk of lung cancer in male smokers. Because of the complex role of neutrophils in lung diseases, we investigated whether carotenoid derivatives could affect respiratory burst and apoptosis of human neutrophils purified from peripheral blood. Stimulation of superoxide production was induced by nanomolar and micromolar concentrations of carotenoid cleavage products with aliphatic chains of different length, but not by carotenoids lacking the carbonyl moiety. The stimulatory effect of carotenoid cleavage products was observed in cells activated by phorbol myristate acetate (PMA), while a slight inhibition of superoxide production was noticed with cells activated by the chemotactic tripeptide N-formyl-Met-Leu-Phe (f-MLP). At higher concentrations, carotenoid cleavage products inhibited superoxide production in the presence of both PMA and f-MLP. In the presence of 20 microM carotenoid cleavage products, inhibition of superoxide production was accompanied by DNA fragmentation and increased level of intracellular caspase-3 activity.

β-Carotene breakdown products may impair mitochondrial functions — potential side effects of high-dose β-carotene supplementation

“…Neutrophil apoptosis may be another reason for the diminished superoxide production by neutrophils in the presence of high CBP concentrations. Indeed, 20 AM CBP stimulate intracellular caspase 3 activity and chromatin fragmentation both in neutrophils [87] and in T-lymphoblast cell line [93]. Fig.…”

“…In contrast, at concentrations slightly higher than those required to enhance the cell response, CBP inhibit superoxide production by PMA-activated neutrophils [87]. On the other hand, if the chemotactic peptide f-Met-Leu-Phe is used instead of PMA to trigger neutrophil response, inhibition of superoxide production is observed even at micromolar concentrations of CBP.…”

“…Stimulation of superoxide production in PMA-activated cells is induced by low concentrations (1 AM) of CBP with aliphatic chains of different length (retinal, h-ionone, CBP), but not by the precursor carotenoids lacking carbonyl moiety (BC or lycopene) [87]. The stimulatory effect is accompanied by a reduction of the lag phase of cell response, which follows PMA stimulation.…”

Carotenoid intake does not affect immune-stimulated oxidative burst in greenfinches

“…Probably the best example of protection conferred by carotenoids against damage generated by phagocytes originates from the study of Staphylococcus aureus, where a mutant strain with disrupted carotenoid synthesis was less able to resist a neutrophil oxidative burst (Liu et al, 2005). Adding different carotenoids to mammalian inflammatory cell cultures can remarkably inhibit oxidative burst (Murakami et al, 2000;Siems et al, 2003;Walrand et al, 2005). Further, dietary carotenoid supplementation can impair the phagocytosis ability of avian blood (McGraw and Klasing, 2006) and suppress inflammation (Koutsos et al, 2003;Koutsos et al, 2006;Meriwether et al, 2010;Shanmugasundaram and Selvaraj, 2011).…”

Induction of Apoptosis by β-Carotene and Dimethyl Tetrasulfide Assisted by UVA Irradiation in HL-60 Cells

“…However, in contrast to our data here, other studies have indicated that exposure to a mixture of -carotene breakdown products induced cytotoxicity and apoptosis in normal animal cells. 14,15) Most of these breakdown products were prepared by hypochlorous acid, and the effects of the photodegradation products of carotenoid prepared by UVA irradiation are largely unknown. The breakdown products induced by hypochlorous acid could be different from the photodegradation products of carotenoids formed by UVA irradiation, so that some of the breakdown products may show cytotoxicity in normal cells.…”