Deoxynivalenol alters circulating and splenic leukocytes and cell migration markers in interaction with time course and sex in young and old BALB/c mice

Abstract

Deoxynivalenol (DON), produced by Fusarium graminearum and Fusarium culmorum, is commonly found in wheat, corn, oats and barley. We hypothesize DON exposure could change leukocyte subset number and their migration potential in peripheral blood with interaction of age and sex, which could be sensitive biomarkers to predict DON exposure for human epidemiological screening. The first mouse study was done in 6-7 week old BALB/c mice. Peripheral blood (PB) and splenic leukocytes were stained and detected by flow cytometry. The results showed the percentage of B cells (CD19 +) in PB was reduced in both sexes at 1.0 and 2.0 ppm at 14 d, with no reduction of B cells after 28 d. Monocytes (CD11b +) in PB and macrophage cells (CD11b +) in spleen were decreased in female BALB/c mice at 1.0 and 2.0 ppm after 28 d, which suggested sex hormones interacted with DON immunotoxicity. No toxicity was observed at doses 0.5 ppm or less. The second mouse study was done in 2-3 month old and 16 month old BALB/c mice. Granulocytes in both ages and sexes were increased at 1.0 and 2.0 ppm DON at 14 d, but normalized after 28 d. Percentage of T helper cells in PB was decreased in young female mice fed 2.0 ppm DON after 14 d, not after 28 d. Percentage of CXCR5 + B cells was decreased in old female mice fed 2.0 ppm DON after 14 d, but not after 28 d. CD29 + CD11a + neutrophils were increased at 1.0 and 2.0 ppm DON in old male mice after 14 d, but no difference was observed after 28 d. CCR9 + T cytotoxic cells were increased in old male mice fed 2.0 ppm DON after 28 d. Taken together, these results suggested DON inhibited T helper cells in young female mice and interrupted B cell, neutrophil and T cytotoxic cell migration potentials in old mice. Most DON toxicity was transient, and interacted with age and sex. In conclusion, the surface markers of leukocytes in PB were changed in BALB/c mice fed 1.0 ppm and 2.0 ppm DON. Age and sex interacted with DON exposure. Most of the effects of DON were temporary, which suggested BALB/c mice adapted to DON exposure. CHAPTER GENERAL INTRODUCTION Research questions Immune system and intestine are the two main targets after DON exposure. Few studies reported the effects of subchronic low doses of DON, which simulated real human exposures in comparison with advisory guidelines for DON ranging from 0.5-2 ppm across the EU, Canada, China and US (Landgren 2005). In our lab, a previous study found 1.0 ppm DON plus 0.9 ppm 3-Ac DON and 2.0 ppm DON plus 1.8 ppm 3-Ac DON inhibited peripheral blood lymphocytes in male BALB/c mice after 28 d (Landgren 2005), which suggested peripheral blood leukocytes could be sensitive biomarker to predict low dose of DON exposure in human epidemiological study. The current mouse studies were to find sensitive biomarkers in peripheral blood to predict low dose of immunotoxicity of DON. General markers used in order to determine if DON inhibits T helper, T cytotoxic, B, monocytes and neutrophils were CD4, CD8, CD19, CD11b, and CD11b + (granulocytes), respectively. CD11b is also a ma...