For a very long time, we studied the metallophilic macrophages of the rodent thymus and in this review our results on morphological, histochemical, enzymehistochemical, immunohistochemical, ultrastructural and functional features of these cells, as well as the molecular regulation of their development, will be presented. Furthermore, the differences between species will also be discussed and the comparisons with similar/related cell types (metallophilic macrophages in the marginal sinus of the spleen, subcapsular sinus of the lymph nodes and germinal centers of secondary lymphoid follicles) will be made. Metallophilic macrophages are strategically positioned in the thymic cortico-medullary zone and are very likely to be involved in: (i) the metabolism, synthesis and production of bioactive lipids, most likely arachidonic acid metabolites, based on their histochemical and enzymehistochemical features, and (ii) the process of negative selection that occurs in the thymus, based on their ultrastructural features and their reactivity after the application of toxic or immunosuppressive/immunomodulatory agents. Taken together, their phenotypic and functional features strongly suggest that metallophilic macrophages play a significant role in the thymic physiology.
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