DISTINCT CHARACTERISTICS OF INITIATION OF THE CLASSICAL AND ALTERNATIVE COMPLEMENT PATHWAYS BY CANDIDA-ALBICANS

Candida albicans is a potent activator of the complement system. The o bjective of this study was to characterize factors that influence the kinetics for activation of C3 and binding of C3 fragments to C. albica ns. Factors that were examined included the surface properties of the yeast and contributions of the classical and alternative complement pa thways. The results showed that incubation of hydrophobic, hydrophilic , or germinating yeast cells in normal human serum (NHS) containing ra diolabeled C3 led to immediate accumulation of C3 on all three cell ty pes, although the rate of accumulation of C3 on germinating cells was lower. An examination of the sites for early C3 binding showed that cl assical pathway initiation led to immediate, synchronous binding over the entire cell surface. A blockade of the classical pathway by absorp tion of putative classical pathway initiators or by chelation of calci um limited activation to the alternative pathway. Binding of C3 solely via the alternative pathway was characterized by a significant lag in the initial binding kinetics. In the absence of classical pathway ini tiation, the early cellular sites for C3 binding appeared as random, a synchronous foci of C3 that appeared to expand with time. The factor(s ) mediating rapid deposition of C3 that was characteristic of the clas sical pathway initiation was reciprocally cross-absorbed by hydrophili c and hydrophobic C. albicans but was not removed by absorption of NHS with Saccharomyces cerevisiae, encapsulated Cryptococcus neoformans, or nonencapsulated C. neoformans. Delayed binding of C3 produced by ab sorption of serum was largely reversed by addition to the absorbed ser um of immunoglobulin G isolated from NHS, indicating a significant rol e for a naturally occurring anti-C. albicans immunoglobulin G in class ical pathway initiation.