MECHANISMS GENERATING FUNCTIONALLY HETEROGENEOUS MACROPHAGES - CHAOS REVISITED

Macrophage populations exhibit a wide range of antigenic and functiona l phenotypes, including cytokine production, response to immunomodulat ory stimuli, and clearance of pathogens. The expanding clinical exploi tation of recombinant growth factors and cytokines with the potential to regulate the production and function of peripheral macrophage popul ations necessitates an increased understanding of the mechanisms by wh ich functionally distinct macrophage populations arise as well as the ramifications of macrophage heterogeneity. The present review summariz es recent data which supports multiple mechanisms by which heterogeneo us macrophage populations arise: 1) differential signals experienced w ithin diverse tissue microenvironments; 2) developmentally-staged expr ession of specific functions; 3) clonal variation of myeloid progenito r cells; and 4) alternate hematopoietic stimulation. These data show t hat the above processes arc not mutally exclusive and that each likely contributes to the observed heterogeneity of peripheral macrophage po pulations.