Macrophages--proliferation, activation, and cell cycle proteins.

Our understanding of mammalian cell proliferation has increased enormously over the past decade. A major advance has been identification and characterization of cyclins and their catalytic partners, cyclin-dependent kinases (cdks). The following brief review highlights the role of macrophages as a cell model for many of the major advances in this field. Macrophages were central to the identification of D-type cyclins and cdk4. In addition, it appears the first work showing that cell cycle proteins are the targets for anti-proliferative agents was performed in macrophages. In these latter studies, and a number of subsequent studies in other cell types, it was shown that many antimitogenic agents repressed cyclin and/or cdk expression. However, recent work in this laboratory suggests macrophage D-type cyclins may also be involved in processes other than proliferation. We have unexpectedly found that macrophages treated with lipopolysaccharide (LPS) express high levels of cyclin D2, even though LPS simultaneously represses cyclin D1 levels and potently blocks proliferation. These data, and those showing the yeast extract Zymosan A also raises cyclin D2 levels, suggest cyclin D2 plays a role in macrophage activation.