VARIABLES AFFECTING PRODUCTION OF MONOCYTE CHEMOTACTIC FACTOR-1 FROM HUMAN-LEUKOCYTES STIMULATED WITH CRYPTOCOCCUS-NEOFORMANS

The chemokine monocyte chemoattractant protein 1 (MCP-1) is produced p redominantly by mononuclear phagocytes and stimulates recruitment into infected tissues of blood monocytes and T cells, These cell types are thought to be critical to host defenses against infections due to Cry ptococcus neoformans, a major cause of disease in persons with AIDS an d other disorders of cell-mediated immunity, Accordingly, in the prese nt study, we examined the conditions under which human monocytes and b ronchoalveolar macrophages (BAM) are stimulated by C. neoformans to pr oduce MCP-1. C. neoformans was a potent inducer of MCP-1 release from monocytes, with levels of chemokine secreted similar to that seen foll owing stimulation with lipopolysaccharide (LPS), BAM, in contrast, wer e stimulated by LPS, but not by C, neoformans, to secrete MCP-1, A pea k in MCP-1 mRNA was seen 8 h following cryptococcal stimulation of mon ocytes, Nine strains of C. neoformans stimulated monocytes to release MCP-1, and there was only modest variation between strains, However, w hen an individual strain was used, the capacity of C. neoformans to st imulate monocyte MCP-1 release did vary, depending upon the conditions used to grow the fungal stimuli, Finally, C. neoformans stimulated co mparable quantities of MCP-1 release in monocytes from donors with and without human immunodeficiency virus infection, These data establish C. neoformans as a potent stimulator of MCP-1 in monocytes, but not in BAM, The failure of C. neoformans to stimulate MCP-1 in BAM, if occur ring in vivo, could result in a diminished cell-mediated inflammatory response following inhalation of airborne fungi.