Tissue macrophage heterogeneity: Issues and prospects

The vast majority of macrophages in the body are present in tissues outside the circulation, yet their remarkable phenotypic heterogeneity within different anatomical compartments in the steady state and disease remains essentially unexplored. The development of immunocytochemical and fluorescent histological methods has revealed the presence and morphological diversity of macrophages within tissues, especially in the mouse, but functional specialisation in situ is difficult to establish and their mechanistic basis remains unknown, particularly in humans, in spite of the rich material available. In this review, we consider some of the technical issues that hamper investigation, assess the contribution of cell differentiation and modulation to macrophage heterogeneity within tissues and illustrate variation of macrophages and closely related cells in selected organs in mouse and man.