Immunomodulating influence of titanium dioxide on the blood leukocytes phenotype

Aliakhnovich N.S., Yanchenko U.V., Rebkavets D.A., Novikov D.K.

Vitebsk State Medical University, Vitebsk

Aim. To study the effect of TiO2 on the blood leukocyte phenotype.

Materials and research methods. The effect of 0.0005 and 0.005 mg/ml TiO2 on the expression of CD3, CD4, CD8, CD25, CD69, CD154, IL10 bound to the receptor on T-lymphocytes; CD19 on B lymphocytes; CD14 on monocytes; CD63, CD203c on basophils; FcεRI receptor on eosinophils was studied in 33 people: 13 – with acute urticaria, Quincke's edema, exacerbation of bronchial asthma (BA), 12 – with BA and / or chronic urticaria without exacerbation, 8 – control group. Phenotyping was carried out after incubation of whole blood with TiO2 for 1 hour at 20 ° C.

Results. Adding a TiO2 suspension to whole heparinized blood dose-dependently reduced the expression of CD4 on CD25--T-cells (p<0.01), CD8 on CD25--T-cells (p<0.05), CD14 on monocytes (p<0.001). 0.005 mg/ml TiO2 increased the number of CD154+-T cells (p <0.01), decreased the expression of CD19 on CD154--B cells (p<0.05) and the density of IL10 associated with the receptors on CD19--lymphocytes (p<0.001).

In acute allergic patients the number of CD19+CD154--B-lymphocytes in blood was higher (p=0.027), and the expression of CD69 on CD154--T-lymphocytes was lower (p=0.027) than in the control. In the presence of both TiO2 concentrations and in the initial samples in acute allergic patients the expression of CD154 on T-lymphocytes was lower than in patients with chronic allergy without exacerbation (p<0.05). The addition of 0.0005 mg/ml TiO2 increased the expression of CD14 on monocytes (p<0.05) in chronic allergy, both concentrations decreased the number of CD14+-monocytes (p<0.05) in acute and chronic allergopathology compared with the healthy control.

In the group of frequently contacting with TiO2, an increased number of FcεRI+-eosinophils and a receptor-associated IL10 density on lymphocytes were detected both under the influence of both TiO2 concentrations (p <0.05) and in the initial samples (p<0.05). 0.005 mg/ml TiO2 increased the relative amount of CD3+CD45+-T cells (p=0.022), 0.0005 mg/ml TiO2 increased the density of CD19 on CD154--B-cells (p=0.037), and both concentrations stimulated the expression of CD69 on CD154--T-lymphocytes (p<0.05) in the group often in contact with TiO2, compared with the control.

Conclusion. TiO2 had an immunomodulatory effect on the blood leukocyte phenotype in vitro, inhibiting the expression of the main markers of blood leukocytes (CD4, CD8, CD14, CD19, the density of IL10 associated with receptors), but increasing the number of active CD154+-T-lymphocytes. In acute allergopathology there was an increased level of CD19+CD154--B-lymphocytes and a reduced level of CD14+-monocytes in the blood, in chronic – an increased expression of activation markers (CD69 and CD154) on T-lymphocytes and CD14 on monocytes. The constant contact with TiO2 in vivo increased the number of FcεRI+-eosinophils and the expression of CD19 on CD154--B-lymphocytes, CD69 on CD154--T-lymphocytes, CD3CD45 on T-lymphocytes and IL10 associated with receptors, on CD19 - lymphocytes.