MECHANISM OF INTRACELLULAR CANDIDACIDAL ACTIVITY MEDIATED BY CALCIUM IONOPHORE IN HUMAN ALVEOLAR MACROPHAGES

In the present study, we investigated the effect of in vitro treatment with calcium ionophore (A23187) on candidacidal activity of human alv eolar macrophages (AM) from normal subjects. In vitro incubation of AM with A23187 results in a significant dose-dependent enhancement of ca ndidacidal activity. The availability of Ca2+ and Mg2+ ions in the cul ture medium is crucial for phagocytosis and killing to occur, but appe ars irrelevant for the binding between Candida albicans and AM. Enhanc ement of the killing effect mediated by A23187 does not correlate with increased phagocytic activity; in fact, the availability of ions is r equired for the phagocytic event, but an increase of cations does not correlate with enhancement of this activity. On the contrary, the augm entation of killing activity correlates with increased production of s uperoxide anion. Moreover, soluble material endowed with candidacidal activity has been extracted from cytoplasmic granules of AM both unsti mulated and following A23187 treatment in vitro. Indeed, the granules extracted contain cationic proteases and, when isolated from stimulate d cells, appear to be significantly more cytotoxic for C. albicans wit h respect to those obtained from unstimulated AM. In conclusion, the r esults reported here show that the phagocytic and killing events are i on dependent and the enhancement of intracellular candidacidal activit y mediated by A23187 in AM is correlated with an augmented anti-Candid a activity of cation-activated proteases.