Pseudomonas respiratory infection in cystic fibrosis: a possible defect in opsonic IgG antibody?
Chronic Pseudomonas aeruginosa infections of the respiratory tract of people with cystic fibrosis (CF) usually are impossible to eradicate and greatly influence their health and longevity. General mechanisms of host defense are not impaired in this disease, except that serum does not support optimal phagocytosis of pseudomonas bacteria by alveolar macrophages and lung ciliary clearance is diminished, perhaps because of the accumulation of tenacious, purulent secretions in bronchiectatic airways and not by a defect in cilia structure or inhibitors of ciliary function. To investigate the defect in phagocytosis, we postulated that opsonic antibody might not be functioning well. Samples of purified IgG antibody against the typical strain of mucoid pseudomonas were prepared on immunoadsorbents, using CF sera and normal sera from volunteers previously immunized with a pseudomonas vaccine. CF IgG opsonin was found to agglutinate and coat well pseudomonas, but not to adhere or attach well to the surface of human alveolar macrophages, hence a defect in the function of the Fc portion of IgG was noted. In extending this analysis to CF lung secretions obtained by bronchoalveolar lavage, IgG antibody was purified exactly as from serum. Although this IgG had good agglutinating activity, much of it was fragmented (5 S size) and found to lack its Fc portion. It was evident that proteolytic enzymes in the purulent lavage secretions could cleave IgG. This activity was localized to a metallo-proteinase elaborated by the mucoid strain of pseudomonas. Thus, CF IgG may have reduced opsonic antibody function because of a molecular change in the Fc portion; this defect is magnified in the infected CF lung where a bacterial protease can actually fragment IgG and further impair its opsonic activity which is already marginal.
D003550:Cystic Fibrosis / Q000150:complications / Q000276:immunology*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D009895:Opsonin Proteins / Q000276:immunology; D010587:Phagocytosis; D011552:Pseudomonas Infections / Q000209:etiology / Q000276:immunology*; D012141:Respiratory Tract Infections / Q000276:immunology*
D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D009895:Opsonin Proteins