Functional characteristics of murine macrophages responding to migration inhibitory factors.

Mouse bone marrow cells differentiate in culture in the presence of L cell-conditioned medium to macrophages (M phi). Proliferation, release of plasminogen activator, expression of transglutaminase, random motility and response to a standard preparation of purified M phi migration inhibitory factor (MIF) was recorded daily up to 14 days. After an initial phase of proliferation, precursor cells differentiated into M phi. In the course of maturation, plasminogen activator production was transiently expressed between day 4 and 12; beginning on day 5 the cells expressed intracellular transglutaminase. Random motility of cells was high at the beginning of culture but steadily declined thereafter. The response to MIF was only expressed between day 5 and 8. However, it was possible to induce MIF responsiveness in mature, unresponsive M phi by the addition of L cell-conditioned medium. To characterize the MIF-responsive M phi type further, bone marrow-derived M phi at day 6 of culture were separated on a hypotonic Percoll gradient into three distinct cell bands. While all densities of M phi displayed random migration, only cells with a density between 1.060 and 1.065 were responsive to MIF. We conclude that the response of M phi to MIF is a phenotypic trait transiently expressed in the course of maturation.