Independence of neutrophil respiratory burst oxidant generation from the early cytosolic calcium response after stimulation with unopsonized Candida albicans hyphae

Abstract

We previously noted differences between neutrophil responses to unopsonized Candida albicans hyphae and responses to other particulate stimuli such as opsonized hyphae or zymosan; these differences include delayed rises in cytosolic calcium ([Ca2+]i), 1,4,5-inositol trisphosphate, and superoxide release and the total absence of early membrane depolarization. Respiratory burst stimulation is required for killing of C. albicans hyphae. Since an early rise in [Ca2+]i may act as a second messenger for burst activation by most agonists, we chelated (Ca2+)i and extraceliular Ca2+ [(Ca2+)e] to compare requirements for superoxide responses to hyphae and other stimuli. Intracellular chelation, which ablated early [Ca2+1i rises, eliminated the fMet-Leu-Phe-induced respiratory burst and profoundly reduced that response to opsonized zymosan (by 96.7%), but chelation of both (Ca2+)i and (Ca2+)e only partially inhibited responses to opsonized and unopsonized hyphae (60.5 and 23.3%, respectively; the latter exceeded absolute responses evoked by opsonized zymosan, a 12-foldmore-potent stimulus for unchelated cells). Simultaneous (Ca2)1 and (Ca2+)e chelation further decreased

Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms

“…This might simply be due to the fact that the susceptibility of microbes to hNGE differs largely. Furthermore, both oxygen-dependent (Wysong et al, 1989;Thompson and Wilton, 1992) and -independent mechanisms (Reeves et al, 2002;Newman et al, 2005) or the collaborative action of both (Hii et al, 1999) have been reported to be important for candidacidal activity of neutrophils underscoring the importance of oxidative killing mechanisms. However, in this study we focused on NET-mediated killing of C. albicans.…”