Imazalil at high plasma concentrations: implications for neutrophil immunophenotype

Neutrophil functions are tightly regulated by numerous membrane receptors, the activation of which determines the appropriate response to various endogenous and exogenous factors. Accumulating evidence indicates that environmental endocrine-disrupting chemicals (EDC) can modulate immune system function, inter alia, by influencing neutrophil activity. Imazalil (IMZ), an EDC known to exhibit antagonistic activity against the androgen receptor expressed on neutrophils, exemplifies a compound that may potentially affect these processes. The aim of this study was to evaluate the effect of imazalil and testosterone on the expression of CD molecules associated with fundamental neutrophil functions. Whole blood collected from healthy men served as the study material. Plasma imazalil concentrations were determined using GC-MS. Isolated neutrophils were incubated in the presence of IMZ (at a concentration established in the present study: 28 ng/ml) or testosterone (at a physiological concentration). Cytometric analysis revealed that exposing cells to imazalil resulted in an elevated percentage of neutrophils expressing CD14, CD66b, CD62L, and CD284, accompanied by a decrease in the percentage of cells expressing CD10, CD11c, CD15, CD49d HLA-DR, as well as a reduction in MPO⁺ neutrophils. No changes in the percentage of neutrophils expressing the analyzed molecules were observed in the presence of testosterone. In conclusion, imazalil modulates the neutrophil immunophenotype, which may inhibit functions such as adhesion, migration, chemotaxis, and phagocytosis. Consequently, this may predispose individuals exposed to this compound to innate immunity disorders.