A B S T R A C T Pseudomonas aeruginosa infection plays a primary pathogenetic role in the chronic respiratory tract disease of cystic fibrosis (CF) patients. Despite pronounced humoral immune responses, reflected by high levels of antibodies against Pseudomonas in serum and in sputum, the antibodies do not eliminate this bacterium. In the present study we have used affinity chromatography with a lipopolysaccharide substituted immunoadsorbent gel to isolate high titers (meanCF = 1:256) of immunotype specific Pseudomonas IgG antibodies from the sera of nine CF subjects, and have evaluated the functional ability of these antibodies to promote phagocytosis and intracellular killing of P. aeruginosa in an in vitro human alveolar macrophage culture system.The phagocytic and intracellular bactericidal kinetics revealed that CF IgG antibodies function in an inhibitory fashion. Both the rate of phagocytosis (rateCF = 204 cpm/unit time) and absolute bacterial uptakes maximal at 120 min (uptakecF = The cellular and humoral immune systems in subjects with CF appear to function normally (1, 3-5) with one major exception: whole serum appears to interfere with the phagocytic function of alveolar macrophages (AM). Whole serum from homozygous CF patients inhibits the ability of rabbit and human AM to ingest and destroy Pseudomonas bacteria (6-9). This effect has been variously attributed to a serum deficiency, to a heat-labile factor, or more recently, to a heat-stable inhibitory factor in CF sera (6-9). "Bactericidal blocking" antibodies have been suggested as an explanation for the selective inability of CF whole serum to support Pseudomonas bactericidal activity (10).Optimal phagocytosis of Pseudomonas by polymorphonuclear leukocytes (PMN) or AM requires the presence of heat-stable opsonins (11,12), and of the heat-stable opsonins IgG has superior protective activity when compared with secretory IgA or . Murphy et al. (15) have studied the role of complement in the phagocytosis of Pseudomonas by rabbit AM. These authors concluded that specific antibody is required for efficient phagocytosis but that in the presence of an excess amount of antibody (as in CF) complement was not essential to maximize phagocytosis. Similarly, IgG antibodies in convalescent sera have been shown to augment phagocytosis of Pseudomonas even in the absence ofheat-labile (complement) opsonins (16,17). Because of the importance of immune IgG in the phagocytic process, and special constraints in antibody binding to macrophages imposed by specific cell surface receptors (18), it is likely that such an opsonic antibody deficiency would be in the IgG class.While CF patients have a generous antibody response in serum, sputum, and to a lesser degree, in lung lavage fluid to P. aeruginosa somatic antigens, the functional capacity of these specifically purified antibodies has not been studied directly. To investigate the opsonic, phagocytic, and bactericidal properties of P. aeruginosa lipopolysaccharide type-specific IgG opsonins (Pseudomonas antibodies), w...