[Chemical and functional characterization of lymphokines]

Macrophages are heterogeneous with respect to a number of constitutive and inducible functions. In order to study the underlying biological principle, a bone marrow liquid culture system was adopted in which bone marrow cells proliferate and differentiate into macrophages. It was found that maturing macrophages express various constitutive or inducible functions in an ordered sequence. The kinetics of their appearance and disappearance are dependent on the proliferative activity of macrophages. Macrophages in "late" G-1 of the cell cycle express constitutive functions like plasminogen activator production and are inducible by bacterial lipopolysaccharides, Poly I:C and lymphokines to release interferons. The response to lymphokines like migration inhibitory factor (MIF) and chemotactic factors is also transiently expressed during maturation. Using purified MIF, its influence on proliferation, differentiation and activation of macrophages was investigated. The changes induced were monitored following the expression of marker enzymes and of phenotype associated cell surface antigens using monoclonal antibodies. The results showed that functional changes induced by MIF on macrophages are limited and are not related to certain macrophage activating activities (MAF). As determined by flow cytofluorometry, transglutaminase expression and proliferation is consistently down-regulated by MIFs. This together with the shift and the expression of surface antigens indicates that MIFs provide a differentiation signal for a "young" macrophage to become more mature.