Journal of Leukocyte Biology 48:15-26 (1990) © 1990 Wiley-Liss, Inc. Cytoplasmic Components of Natural Killer Cells Limit the Growth of Cryptococcus neoformans

Murine natural killer (NK) cell-mediated inhibition of growth of a yeast-like target cell, Cryptococcus neoformans, was completely abrogated by blocking the effector cell secre-tory process with monensin. Therefore, further studies were performed to determine the ability of various cytoplasmic fractions of NK cells to mediate inhibition of cryptococcal growth. Percoll-fractionated homogenates of rat LGL tumor cells demonstrated that the granule-containing fractions plus three additional sets of less dense cytoplasmic frac-tions displayed anti-cryptococcal activity; whereas only the cytoplasmic granule-con-taming fractions had cytotoxic activity against YAC-1 tumor cell and sheep erythrocyte targets. Maximal cryptococcal growth inhibition induced by LGL granules occurred after a 1 h incubation, required the presence of Ca2 (1.0 mM) or Mg2 (0.5 mM or 5.0 mM), and was completely abrogated in the presence of rabbit anti-LGL granule IgG. Cytolysin, the granule component which mediates tumor cell and sheep erythrocyte lysis, effectively limited the growth of cryptococci. Since Percoll gradient fractionation of the LGL ho-mogenates demonstrated three separate peaks of anti-cryptococcal activity other than the granule peak, it is possible that the cytolysmn-contamning granules are not the only subcellular component of NK cells playing a role in inhibition of C. neoformans growth. Key words: LGL, granules, fungu