Production of superoxide anion, prostaglandins, and hydroxyeicosatetraenoic acids by macrophages from hypersensitivity-type (Schistosoma mansoni egg) and foreign body-type granulomas

Abstract

Macrophages isolated from hypersensitivity (Schistosoma mansoni egg) and foreign body- (Sephadex bead) type granulomas were evaluated with regard to superoxide anion (O2-) production and arachidonic acid metabolism. Granuloma macrophages from schistosome-infected mice were examined during both the acute and modulated phases of the disease. In addition, the populations were characterized phenotypically by measurement of Ia antigen expression. Based on differences in the parameters studied at least three different macrophage populations could be identified in acute, modulated, and foreign body-type lesions, respectively. Macrophages from acute lesions (8-week granuloma macrophages) produced significant amounts of O2-, prostaglandins, and monohydroxyeicosatetraenoic acids without the addition of an exogenous stimulus. These cells also showed a high degree of Ia expression. In contrast, macrophages from modulated (20-week granuloma macrophages) and foreign body (foreign body granuloma macrophages) lesions required stimulation with phorbol ester to evoke significant O2- production and minimally metabolized arachidonic acid. However, 20-week and foreign body granuloma macrophages could be distinguished by their high and low degrees of Ia expression, respectively. The role of lymphokines and other intercellular signals in determining macrophage activation states within granulomas is discussed.