The effect of the lymphokine(s) MIF/MAF on murine macrophage behaviour.

Migration inhibition factor (MIF) was isolated from the mouse, rat, Xenopus laevis and the newt Triturus cristatus. These MIFs were used to investigate the specificity of the molecule and it was found that MIF is not species specific and that animals with an evolutionarily sophisticated immune response are responsive to MIFs produced by animals which show much less complex immune responses. Macrophages are one of the few normal adult cell types which show motility as part of their functional phenotype and this process can by manipulated in vitro by the presence or absence of MIF. Using LM and EM the effects of MIF and substrate on locomotion and macrophage-substrate adhesion were investigated. The question of macrophage heterogeneity was addressed to determine whether macrophages can be activated for a wide range or only a limited number of functions. The results obtained suggest that macrophages become committed along particular pathways depending on external stimuli from the micro-environment surrounding the cell and that performance of particular functions precludes the cell from performing certain other functions. Macrophage activating factor (MAF) co-chromatographs with MIF and was isolated with MIF. The effect of MIF/MAF and effector : target cell ratio on macrophage anti-tumour activity was also investigated. Macrophages were found to have a cytostatic effect at a much lower effector : target cell ratio than that required for cytolysis of transformed cells. Also, macrophages lyse target cells at a lower effector:target cell ratio when cultured on a collagen rather than a glass substrate. Macrophages are also attracted through collagen towards transformed cells preferentially. Pretreatment with MAF enhances the cytolyic response of macrophages. This response is increased further by pretreating macrophages with LPS and MAF when both pretreatment time and sequence are important in determining which functions macrophages perform.