Cytokine-induced human multinucleated giant cells have enhanced candidacidal activity and oxidative capacity compared...

The granulomatous response to infection is characterized by formation of multinucleated giant cells (MGC). A model has been developed for the study of MGC using fresh human peripheral blood monocytes cultured in medium supplemented with autologous serum and a combination of recombinant human interferon-gamma and interleukin-3 (100 units/mL each). Differential Giemsa staining demonstrated a 53% increase in candidacidal activity of MGC (35.1% +/- 2.0% of ingested organisms were killed by MGC) compared with identically cultured mononuclear macrophages (which killed 22.9% +/- 1.8% of organisms ingested; P less than .05). There was no significant difference in the number of organisms ingested. MGC stimulated with phorbol myristate acetate produced 2.2 times as much superoxide anion per unit of cytoplasmic protein as identically cultured and stimulated macrophages (34.3 vs. 16.2 nmol of superoxide/microgram of cell protein; P less than .01). This was corroborated with single-cell measurements of oxidative activity using digital image analysis. These observations support the hypothesis that MGC have an advantage in microbicidal activity over macrophages that may be due, at least in part, to enhanced oxidative capacity.