Tompkins, Joanne Deborah (1997) The uptake of heavy metals into human phagocytes. University of Southampton, Doctoral Thesis.
Abstract
Zinc has already been shown to enter a variety of different cell types and so experiments have been carried out in an attempt to determine how zinc enters human blood neutrophils and human lung macrophages. Zinc has already been shown to enter red blood cells through the anion exchanger and so experiments were carried out to investigate whether the same occurred in neutrophils and macrophages. The results suggested that approximately half the amount of zinc taken up into the neutrophils entered the cell through the anion exchanger. Amino acids, particularly histidine, have been shown to facilitate zinc uptake into other cell types, therefore experiments were carried out in the presence of histidine. Both L- and D-histidine stimulated zinc uptake so the effect was not stereospecific. Cells were also stimulated with four different stimuli to determine the effect this had on zinc uptake. This showed that on stimulation with PMA, fMLP, A23187 and ionomycin, cells accumulated more zinc. Further experiments were carried out with calcium channel inhibitors to ascertain whether calcium channels were involved and other inhibitors were used to study their effect on zinc uptake. The effect of cadmium on zinc uptake was also analysed. Cadmium uptake into neutrophils was investigated by carrying out experiments similar to those carried out to study the mechanism of zinc uptake. These showed that cadmium did not enter the neutrophil through the anion exchanger and it was not transported as part of a cadmium-histidine complex. As with zinc, on cell activation with PMA, A23187 and ionomycin, neutrophils accumulated more cadmium. Stimulating cells with fMLP did not lead to an increase in cadmium uptake. The accumulation of both zinc and cadmium into human lung macrophages was also investigated. Both zinc and cadmium appeared to enter the macrophage through the anion exchanger, but the results did not reach statistical significance.
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