1-Thiocarbamoyl-2-imidazolidinone (TCI) inhibits immune interferon-induced expression of Ia antigen on cultured mouse peritoneal macrophages, a discovery that could explain the unusual immunopharmacological effect of TCI on cellular and humoral immunity. Our goals now are to elucidate the specificity and possible mechanism(s) of action of this extremely potent agent.
Specific aims are to 1) characterize the effects of TCI on immune interferon-induced changes in Ia expression by macrophages, 2) determine whether TCI affects other immune interferon-induced responses and certain immune interferon-independent induced properties of macrophages, 3) ascertain whether TCI mediates its effects via cell surface receptors and explore receptor interactions between TCI, immune interferon and other relevant mediators, and 4) identify intracellular biochemical processes that are affected by TCI alone or in combination with immune interferon and/or other mediators. Responses of a macrophage-like tumor cell line, e.g. P388D1, to immune interferon and TCI will be studied; parameters perturbed by the lymphokine and affected by TCI are most likely to relate to the latter's mode action. Changes in cell surface protein expression will be monitored by immunofluorescence, radio-immunoassay and flow cytometry. Other macrophage functions to be examined include abililties to generate a respiratory burst, phagocytize opsonized particles and present antigen to target cells. 3H-TCI of high specific radioactivity will be used to study cellular transport of TCI, identify putative TCI """"""""receptors"""""""" in whole cells and membrane preparations, and elucidate binding interactions between TCI, immune interferon and/or other mediators. This research should provide basic information about the immunomodulatory actions of immune interferon and TCI as well as suggest appropriate clinical applications for TCI.
