Effect of Mycotoxins on Some Activities of Isolated Human Neutrophils

Abstract

Activities of mycotoxins--citrinin, ochratoxin B, rubratoxin B, and zearalenol beta--that affected superoxide anion (O2-) production were studied on human neutrophils with regard to hypochlorous acid (HOCl) generation, nitric oxide (NO) formation, and chemotaxis of isolated cells. At the doses of 10(-8), 10(-6), 10(-4), or 10(-2) mg/mL, in stimulated cells the mycotoxins inhibited HOCl production proportionally to that of O2- because HOCl production is directly dependent on O2- generation. But unlike the others, zearalenol beta decreased HOCl production much more than one of O2-, indicating an effect also on myeloperoxidase secretion. All mycotoxins inhibited NO generation but only at the dose of 10(-2) mg/mL. Formyl-met-leu-phe-induced chemotaxis of neutrophils was deeply affected as well, as all mycotoxins at all doses used decreased it. All considered effects were not dose-dependent, likely connected to high variability of individual sensitivity to these compounds and because they already are present in blood introduced with foods. These activities of neutrophils confirm and extend the danger for immune systems by mycotoxins also in very small quantities, since the smaller concentrations we used are easily reachable in blood.

Application of omics to immunotoxicology : from mechanisms of action to alternative testing strategies

“…Another gene that was downregulated by ochratoxin A, PLCG2, has been linked with leukocyte migration before: a patient carrying a missense mutation in PLCG2 had impaired leukocyte chemotaxis (Zhou et al, 2012). Our results are in concordance with those of Richetti et al, who demonstrated that several mycotoxins, including ochratoxin B, are potent inhibitors of chemotactic peptide-induced chemotaxis of human primary neutrophils (Richetti et al, 2005).…”

Deoxynivalenol impairs the immune functions of neutrophils

“…Using formyl-Met-Leu-Phe as chemoattractant, an inhibitory effect of ochratoxin B and zearalenone was observed at low concentration (3 nM to 30 M) on the chemotaxis of human neutrophils [16]. A previous study showed that the random migration of porcine neutrophils was not affected by low concentrations (0.1-10 M) of DON [17] suggesting that DON interfered with the signal between chemoattractant and the PMNs but did not affect the capacity of PMNs to move in the surroundings.…”

“…Immune cells are a primary target for DON, and depending on the dose and frequency of exposure, DON can be either immunosuppressive at high concentration or immunostimulatory at low concentration. The immunomodulatory effects of DON have been described on a macrophage cell line , natural killer cells , lymphocytes , and dendritic cells but very few studies have investigated the effect of DON on polymorphonuclear cells (PMNs) . PMNs constitute the first line of defense against intruding microorganisms.…”

Fungal Toxins and Host Immune Responses

“…Notably however, the phagocytic ability of neutrophils was significantly reduced after 17 days (Müller et al, 1995), suggesting that cellular function was impaired. Application of ochratoxin A to human neutrophils in vitro stimulated a dose-dependent activation of the oxidative burst response from 2 h, an increase in the level of intracellular calcium from 4 h and adenosine triphosphate depletion and necrosis from 8 and 20 h, respectively (Kupski et al, 2016), while 25 µM treatment impaired chemotactic and NO responses (Richetti et al, 2005).…”