PART I. BASIC MECHANISMS OF SARCOIDOSIS zyxw Functional Aspects of Mononuclear Phagocyte Involvement in Lung Inflammation" DAVID W. H. RICHES AND PETER M. HENSON Department of Pediatrics National Jewish Hospital and Research Center Denver, Colorado 80206 INTRODUCTION zyxw Macrophages, which constitute part of the mononuclear phagocyte system, are found in varying numbers in almost all mammalian tissues and organs. Elements of the mononuclear phagocyte system include the fixed macrophages that line the vascular beds of such organs as the liver and spleen, and the mobile resident macrophages that reside on the serous membrane of the peritoneum and in the alveoli and airways of the lung. Another element of the mononuclear phagocyte system is the mobile, plu- ripotent, blood-borne monocyte which can leave the circulation either randomly, under steady state conditions to populate specific tissues such as the spleen, or selectively, under the influence of a chemotactic gradient to infiltrate an inflammatory site.' Once in the tissues, monocytes acquire the generic morphological and functional charac- teristics of mature macrophages yet adapt to the specific local environment of the tissue into which they have migrated. In view of this potential ubiquity of macrophages, it is perhaps not too surprising to find that these cells have been implicated in a plethora of human diseases ranging from a nonimmunological involvement in atheroma* to a strong immunological in- volvement in rheumatoid arthriti~.~ The objective of this review is to illustrate the pluripotential nature of the macrophage's responses to its environment and to stimuli in these environments with which it is known to interact. Rather than embark on a lengthy description of the many diverse responses ascribed to macrophages (some of which are summarized in FIG. l), however, we will limit our discussion to one aspect of mononuclear phagocyte function, namely its adaptability (that is, its responsiveness) to its environment, particularly in the lung. This adaptability, we believe, contributes importantly to the role the cell plays in the initiation, continuation, and resolution of inflammation. 'This work was supported by United States Public Health Service-National Institutes of Health Grants HL-21565 and GM-24834. zyxwv 6