The mononuclear phagocyte and immunoregulatory effector (M-PIRE) system: evolving concepts

The phagocytic activity of macrophages and related cells has been recognized for over a century. Within the last decade a variety of other functions has been attributed to these same cell types. Examples include antigen processing and antigen presentation to B and T cells, and synthesis of a large number of immunoregulatory proteins. This recent explosion of information regarding the functions and cell types of this complex cell system has had little impact on the practice of pathology in that nomenclature, concepts of disease classification, and our diagnostic approach to the majority of "histiocytic" disorders have not been revised. As the mysteries of this complex cell system are unraveled, older names, such as the mononuclear phagocyte system that focus on only one function, have become obsolete. Because recent evidence shows that this cell system also plays a pivotal and multifaceted role in immunity, the designation mononuclear phagocyte and immunoregulatory effector (M-PIRE) system is recommended. Diverse cell types, including bone marrow precursor cells, histiocytes, various dendritic cells, and Langerhans cells, comprise the M-PIRE system, and these are located in tissues throughout the body. Although mature macrophages and dendritic cells are strikingly different in morphology and function, evidence from studies of both normal cells and proliferative disorders suggests a common cell of origin. There also is provocative evidence suggesting that transitions between cell types may occur, analogous to those observed in the lymphoid cell system. In this report, a conceptual overview of the M-PIRE system including origin, normal function, proposed transitional cell forms, and disease states is presented.