STUDY ON NEWLY IDENTIFIED MICROGLIAL CELL GROWTH FACTORS

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We have been interested in possible physiological roles of thymic myoid cells and succeeded in cloning the cells. During the persent study, we have found that the myoid cells produce various cytokines, such asa IL-1alpha, IL-6, IL-7, an uncharacterized lymphostimulatory factor (s), and two novel monocytic cell growth factors ; the one is purified as a 60-80 kDa factor and the other one is a 100kDa factor. Monocytic lineage cells induced by the two factors were morphologically and phenotypically different from each other and also different from those induced by M-CSF and GM-CSF.Computor search analysis suggests that the 100kDa factor is highly homologous to the core protein of biglycan which has not been identified as a growth factor. Biochemical and biological characterization of the 100kDa factor indicate that the biological activity reside on core protein molecules with the molecular weight of 40kDa, suggesting that glycosaminoglycan and oligosaccharide chains are not important for monocyte growth activity. The 60-80 kDa factor, on the other hand, appeared not to have homology with the authentic cytokines. We have succeeded in cloning 1 kb of the gene. We are currently trying to extend the sequence of the 60-80 kDa gene clone to produce the recombinant factor. We are also interested in analyzing the mechanisms of generation of heterogeneity in monocytic lineage cells. We believe our two factors, together with other cytokines, are important for generation of heterogeneity in monocytic cells. To provide heterogenous monocytic cell populations, such as microglias, Kupffer cells, are probably significant events for defending self from various infections and neoplasms.