The long range goal is to understand how alpha/beta interferons are involved in the regulation of macrophage activation for tumor cell killing. The rationale for undertaking the proposed research is that these interferons undoubtedly induce and modulate macrophage functions by engaging a specific membrane receptor. Investigation of the receptor should, therefore, yield information regarding the early events that are involved in the induction/regulation of macrophage activation. Alpha and beta interferons will be purified to homogeneity using immunoaffinity chromatography as the final step. They will be used to address the following specific aims: (1) determine the extent to which alpha or beta interferon potentiates the development of cytolysis by macrophages primed with gamma interferon and triggered by LPS. These studies will complete the functional characterizations of alpha/beta interferons that we intend to make; (2) characterize the number and binding affinity of alpha/beta interferon receptors on macrophages, both unstimulated and in the stages that lead to full activation. Computer-assisted Scatchard analysis of binding data obtained using radiolabeled beta interferon will be the main approach; and (3) characterize the distribution of alpha/beta interferon receptors on individual macrophages by ultrastructural means, and determine whether or not there are individual differences in the distribution of receptors on cells within a given macrophage population. Unstimulated cells and those in the stages leading to activation will be compared again here. These studies are significant because they will yield new, basic information about an important host defense mechanism, macrophage activation for tumor cell killing. Because alpha/beta interferons mediate a variety of biological effects, undoubtedly through the same receptor, results from the proposed research are likely to have broad biological relevance in addition to the importance they will have in understanding how the alpha/beta interferons are involved in the regulation of macrophage activation for tumor beta interferon receptor on macrophages. (HF)
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| Pace, J L; MacKay, R J; Hayes, M P (1987) Suppressive effect of interferon-beta on development of tumoricidal activity in mouse macrophages. J Leukoc Biol 41:257-63 |
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| Russell, S W; Pace, J L; Varesio, L et al. (1986) Comparison of five short-term assays that measure nonspecific cytotoxicity mediated to tumor cells by activated macrophages. J Leukoc Biol 40:801-13 |
