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 alveolar macrophages (AM) from normal subjects. In vitro incubation of AM with A23187 results in a significant dose-dependent enhancement of candidacidal activity. The availability of Ca2+ and Mg2+ ions in the culture medium is crucial for phagocytosis and killing to occur, but appears irrelevant for the binding between Candida albicans and AM. Enhancement of the killing effect mediated by A23187 does not correlate with increased phagocytic activity; in fact, the availability of ions is required for the phagocytic event, but an increase of cations does not correlate with enhancement of this activity. On the contrary, the augmentation of killing activity correlates with increased production of superoxide anion. Moreover, soluble material endowed with candidacidal activity has been extracted from cytoplasmic granules of AM both unstimulated and following A23187 treatment in vitro. Indeed, the granules extracted contain cationic proteases and, when isolated from stimulated cells, appear to be significantly more cytotoxic for C. albicans with respect to those obtained from unstimulated AM. In conclusion, the results reported here show that the phagocytic and killing events are ion dependent and the enhancement of intracellular candidacidal activity mediated by A23187 in AM is correlated with an augmented anti-Candida activity of cation-activated proteases.
Vecchiarelli
A
A
Department of Experimental Medicine, University of Perugia, Italy.
Dottorini
M
M
Cociani
C
C
Pietrella
D
D
Todisco
T
T
Bistoni
F
F
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002176:Candida albicans / Q000276:immunology*; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D005260:Female; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology*; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010587:Phagocytosis / Q000187:drug effects
D000001:Calcimycin; D015759:Ionomycin; D003513:Cycloheximide; D008274:Magnesium; D003078:Colchicine; D002118:Calcium