title: Complement and experimental respiratory failure.
abstract: Activation of the complement system within the lung can lead to acute pulmonary damage and dysfunction. Based on a variety of experimental models it is now apparent that lung injury is related to complement-induced generation of oxygen derived free radicals from neutrophils and from macrophages. In addition to the oxygen radicals, it is also possible that the conversion of hydrogen peroxide by myeloperoxidase to hypochlorous acid also contributes to the injury. Exposure of the pulmonary microvasculature to oxygen radicals generated from complement-activated neutrophils causes focal damage and necrosis of endothelial cells. IgG immune complex-induced injury of lung is also complement and neutrophil dependent and oxygen radical mediated. In contrast, lung injury produced by IgA immune complexes is neutrophil independent, complement dependent and oxygen radical mediated. There is now increasing evidence that oxygen radicals are not only directly tissue-toxic but also able to potentiate the activity of leukocytic proteases. In all of these models the lung can be protected from injury by pretreatment of the animals with either scavengers of hydroxyl radical or with agents that prevent its formation (e.g. catalase, iron chelators). Data from these models may have direct clinical relevance to conditions such as adult respiratory distress syndrome where lung injury is probably oxygen radical mediated.
mesh_terms: D000818:Animals; D002374:Catalase / Q000627:therapeutic use; D003167:Complement Activation; D005609:Free Radicals; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007502:Iron Chelating Agents / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008264:Macrophages / Q000378:metabolism; D008954:Models, Biological; D009504:Neutrophils / Q000378:metabolism; D011817:Rabbits; D012131:Respiratory Insufficiency / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D012756:Sheep; D013481:Superoxides / Q000378:metabolism / Q000633:toxicity
chemical_list: D005609:Free Radicals; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007502:Iron Chelating Agents; D013481:Superoxides; D002374:Catalase