Human macrophage maturation and heterogeneity: Restricted expression of late differentiation antigens in situ

Summary Terminal maturation of human macrophages is an important step for creation of cell diversity amongst site-specific subpopulations and their functional competence in situ. As monocytes undergo differentiation in vitro, they start to express lineage-restricted antigens specific for differentiation stages beyond the blood monocyte level as detected by monoclonal antibodies of the MAX series. We have analyzed the expression of MAX.1, MAX.2, MAX.3 and MAX.11 on exudate-type macrophages from pleural and peritoneal cavity and the alveolar space, as well as on resident and activated tissue macrophages in cryostat sections of spleen, lymph node, tonsil, liver, gut mucosa, skin, placenta, kidney and bone. It was found that free macrophages in serous cavities expressed MAX antigens in a heterogenous pattern, whereas none of the organ-specific tissue macrophages subsets did so (with the exception being the weak label of MAX.2 on Kupffer cells). Only during allograft rejection were infiltrating macrophages found to express MAX antigens but not at sites of nonspecific inflammation or granuloma formation. However, Cyclosporin A treatment seems to suppress the induction of MAX antigen expression on intragraft macrophages. In addition, freshly harvested MAX-negative exudate macrophages converted to the complete Max⁺ phenotype on further cultivation. Isolated Kupffer cells were able only to express the MAX.2 antigen in culture but still did not react with the MAX.1 and MAX.3 monoclonal antibodies. Some MAX antigens are co-expressed on glomerular mesangial cells, dendritic reticulum cells and placental cells (MAX.1/. 11) as well as on capillary endothelium within tissues of active immune response (MAX.2). These results add to the knowledge of the phenotypic heterogeneity within the macrophage system as a result of site-specific influences and modulation during a cell-mediated immune response. They also give evidence for a major difference between free exudate-type macrophages and resident tissue macrophages.This work has been supported by Deutsche Forschungsgemeinschaft (AN111) and Boehringer Ingelheim Fonds Stiftung für Grundlagenforschung, Stuttgart, FRGReinhard Andreesen is a recipient of a Heisenberg Award from the Deutsche Forschungsgemeinschaft