title: Membrane attack complex of complement and neutrophils mediate the injury of acid aspiration.
abstract: A significant role for the alternative complement pathway in acid aspiration has been demonstrated by the observation that C3 genetic knockout mice are protected from injury. Utilizing C5-deficient mice, we now test the role of the terminal complement components in mediating injury. Lung permeability in C5-deficient mice was 64% less than in wild-type animals and was similar to wild-type mice treated with soluble complement receptor type 1, which gave a 67% protection. Injury was fully restored in C5-deficient mice reconstituted with wild-type serum. The role of neutrophils was established in immunodepleted wild-type animals that showed a 58% protection. Injury was further reduced (90%) with the addition of soluble complement receptor type 1, indicating an additive effect of neutrophils and complement. Similarly, an additional protection was noted in C5-deficient neutropenic mice, indicating that neutrophil-mediated injury does not require C5a. Thus acid aspiration injury is mediated by the membrane attack complex and neutrophils. Neutrophil activity is independent of C5a.
authors.affiliation: Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: C
authors.initials: C
authors.lastname: Kyriakides
authors.forename: W
authors.initials: W
authors.lastname: Austen
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Favuzza
authors.forename: L
authors.initials: L
authors.lastname: Kobzik
authors.forename: F D
authors.initials: FD
authors.lastname: Moore
authors.forename: H B
authors.initials: HB
authors.lastname: Hechtman
mesh_terms: D000818:Animals; D003176:Complement C3 / Q000378:metabolism; D003182:Complement C5 / Q000737:chemistry / Q000172:deficiency / Q000235:genetics; D015936:Complement C5a / Q000502:physiology; D015938:Complement Membrane Attack Complex / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009504:Neutrophils / Q000502:physiology*; D011015:Pneumonia, Aspiration / Q000503:physiopathology*; D011650:Pulmonary Alveoli / Q000378:metabolism
chemical_list: D003176:Complement C3; D003182:Complement C5; D015938:Complement Membrane Attack Complex; D015936:Complement C5a