Enhancement of human eosinophil-mediated killing of Schistosoma mansoni larvae by mononuclear cell products in vitro

Previous studies have shown that eosinophils from eosinophilic individuals differ functionally from those of normal individuals. In order to test whether agents that might induce eosinophilia could also affect eosinophil function, we have compared the capacity of culture supernatants from mononuclear cells of eosinophilic or normal individuals to enhance eosinophil activity, as reflected by an increased killing of schistosomula of Schistosoma mansoni in vitro. An enhancing activity was detected, which increased both the antibody- dependent, and to some extent the antibody-independent killing of schistosomula by eosinophils, in the absence of complement. Under similar conditions, the supernatants failed to stimulate an otherwise undetectable neutrophil-mediated killing. The activity could be removed from the assay by washing, without reversing previous eosinophil stimulation, and was not directly toxic to the schistosomula. Preliminary characterization of the activity indicated that it was relatively heat-stable at 100 degrees C for 30 min, and had an estimated molecular weight of 35,000-45,000 as judged by G-200 Sephadex fractionation. The activity was produced by a nonlymphocytic, nonspecific esterase-containing adherent mononuclear cell in the absence of either Con A or antigenic stimulation. Significant enhancing activity was detectable after 1 h of culture and continued for at least 25 h. Protein synthesis was required for its production or release. Although the activity was detectable in supernatants from both eosinophilic and normal individuals, the supernatants that demonstrated highest activity and that could be titrated out furthest were generally derived from eosinophilic individuals, suggesting that there might be some association between eosinophilia and enhanced eosinophil function.