INCREASED C3 PRODUCTION IN HUMAN MONOCYTES AFTER STIMULATION WITH CANDIDA-ALBICANS IS SUPPRESSED BY GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR

Activation of the complement system is an important part of host resis tance against fungal infections. When human monocytes, cultured for 2 days or more, were treated in vitro with Candida albicans for 24 h, an enhancement of their biosynthesis of the complement components C3 and factor B was found. However, when C. albicans was administered to fre shly isolated monocytes, a consistent stimulation of factor B biosynth esis occurred, while the C3 production was increased in about 50% of t he donors. C. albicans also induced the release of granulocyte-macroph age colony-stimulating factor (GM-CSF) from the cultured cells, appare ntly in larger amounts in the donors in whom no stimulation of C3 prod uction was found. An antibody to GM-CSF administered with the yeast at the initiation of the monocyte culture caused an increase in the C3 p roduction. Furthermore, when monocytes were treated with recombinant h uman GM-CSF either at the same time as or 4 days prior to the addition of C. albicans, the increase in C3 production was suppressed or neutr alized, while factor B biosynthesis was unaffected. Taken together, th ese results indicate that monocytes respond to C. albicans with an inc reased production of complement factors. This may be an important mech anism both for opsonization of the fungus and for initiation of an inf lammatory reaction. At an inflammatory site, this complement response may be suppressed by locally produced GM-CSF.