Mononuclear Phagocytes from Carrageenan-induced Granulomas

It is now accepted that macrophages play an integral role in chronic inflammatory processes (1, 2). They are always present at sites of chronic inflammation, albeit in widely varying proportions, accompanied by a variety of other cell types. The cellular composition of chronic inflammatory lesions is dependent on the nature of the inciting stimulus. The lesions of many clinically important chronic inflammatory diseases such as rheumatoid arthritis are dominated by lymphocytes (3). Some stimuli, e.g. mycobacteria (4) and the intracellular parasites Listeria monocytogenes (5) and Toxoplasma gondii (5) provoke lesions rich in macrophages but also with prominent lymphoid cell components. Lesions caused by indigestable materials such as asbestos (6) and the cell walls of group A streptococci (7, 8) are dominated by macrophages with minimal contribution by cells of the lymphoid system. Carrageenan is a long chain polysaccharide containing various salts of sulfate esters and is derived from Irish sea moss, Chondrus crispus (9). After being used by Robertson and Schwartz (10) as a stimulus for chronic inflammation, carrageenan has subsequently been used extensively as a model stimulus of both acute (11, 12) and chronic inflammation (13, 14). Chronic inflammatory lesions caused by carrageenan are dominated by macrophages, which have been shown to persist at these sites for prolonged periods of time (15, 16). Although it is likely that these cells are primarily responsible for the formation and evolution of carrageenan granulomas, very little is known about those biochemical properties which allow them to mediate these changes. Some studies with explants of carrageenan granulomas have demonstrated the secretion of collagenase (17) while short-term suspension cultures of such disrupted tissue have been shown to incorporate amino acids and metabolize glucose (18). Clearly, such cells can be characterized best by examination of their properties utilizing stable populations of the dissociated cells in tissue culture. This paper describes such studies which lead us to conclude that cells from carrageenan granulomas can be dispersed enzymatically and maintained in culture and that they display several of the biochemical and functional characteristics used to identify mononuclear phagocytes (19-22).