In vitro and in vivo stimulation of rat neutrophils and alveolar macrophages by immune complexes. Production of O-2 and H2O2.

Rat neutrophils and alveolar macrophages were quantitatively studied for production of O-2 and H2O2 after incubation of cells with immune complexes, and the responses were compared with those produced after cell contact with phorbal myristate acetate or zymosan particles. The production of toxic oxygen products is a linear function of cell number, the duration of incubation, and the amount of immune complex employed. In the case of neutrophils, there is a direct relationship between the amounts of immune complex internalized, secretory release of lysosomal enzymes, and production of O-2 and H2O2. With both neutrophils as well as alveolar macrophages, maximal production of O-2 occurs with the largest complexes (formed under conditions of antigen equivalence). When limiting cell concentrations are used, alveolar macrophages produce considerably more oxygen products than an equivalent number of peritoneal neutrophils obtained from the same animals. Thus, alveolar macrophages as well as neutrophils represent important potential sources for the generation of toxic oxygen products in lung inflammatory reactions. Experiments have also been designed to estimate the relative contributions of neutrophils and alveolar macrophages in vivo during acute immune complex deposition in lung. The data indicate that both neutrophils and alveolar macrophages are activated by in vivo exposure to immune complexes, each cell type producing a 2-4-fold increase (over baseline levels) in the amounts of O-2. Thus, alveolar macrophages as well as neutrophils may play an important role in the generation of toxic oxygen products that have been incriminated in the pathogenesis of acute lung injury following deposition of immune complexes.