Macrophage heterogeneity.

Abstract

Macrophages perform a large number of diverse and on occasion mutually antagonistic functions. It seems unlikely given the magnitude of the task, that any one cell could carry out all these different demands. This raises the possibility that distinct subsets of macrophages exist each capable of performing only certain functions. It is indeed the case that although all macrophages have many features in common they are by no means uniform. Two major types of macrophage heterogeneity have been described. The first is termed "Interpopulation" heterogeneity and refers to differences between populations of macrophages obtained from different tissue sites. The second is termed "Intrapopulation" heterogeneity and refers to differences between subpopulations of macrophages obtained from within a particular site. We propose that such macrophage heterogeneity could be generated by 2 main mechanisms--"Differentiation and Modulation". It is assumed that as macrophages differentiate from bone marrow precursor cells they sequentially express a series of functionally distinct phenotypes. Such phenotypes are however relatively dynamic and may be readily altered by exposure to various microenvironmental and nonmicroenvironmental modulating signals. The responsiveness of cells to modulating signals is likely to depend both on their differentiation stage and previous exposure to other such signals. Assuming that the cells entering different tissue sites are essentially identical, then "Interpopulation" heterogeneity may be generated as a direct result of different microenvironmental modulating signals acting on the cells. "Intrapopulation" heterogeneity on the other hand may be generated by both differentiation and modulation. Macrophages at various differentiation stages are found within a tissue. Some cells will have recently arrived from the blood stream while others may have resided in the tissue for some time. In addition, the cells within a tissue may have been exposed to a different spectrum of modulating signals, or exposed to the same signals for various periods of time. The suggested existence of distinct macrophage sublineages adds an additional level of complexity to the subject of macrophage heterogeneity. It has been shown in a relatively small number of experiments that colonies of macrophages, clonogenically derived from individual bone marrow precursor cells in vitro, may express different phenotypes.(ABSTRACT TRUNCATED AT 400 WORDS)