Experimental murine acid aspiration injury is mediated by neutrophils and the alternative complement pathway.
Acid aspiration may result in the development of the acute respiratory distress syndrome, an event associated with significant morbidity and mortality. Although once attributed to direct distal airway injury, the pulmonary failure after acid aspiration is more complex and involves an inflammatory injury mediated by complement (C) and polymorphonuclear leukocytes. This study examines the injurious inflammatory cascades that are activated after acid aspiration. The role of neutrophils was defined by immunodepletion before aspiration, which reduced injury by 59%. The injury was not modified in either P- or E-selectin-knockout mice, indicating that these adhesion molecules were not operative. C activation after aspiration was documented with immunochemistry by C3 deposition on injured alveolar pneumocytes. Animals in which C activation was inhibited with soluble C receptor type 1 (sCR1) had a 54% reduction in injury, similar to the level of protection seen in C3-knockout mice (58%). However C4-knockout mice were not protected from injury, indicating that C activation is mediated by the alternative pathway. Finally, an additive effect of neutrophils and C was demonstrated whereby neutropenic animals that were treated with sCR1 showed an 85% reduction in injury. Thus acid aspiration injury is mediated by neutrophils and the alternative C pathway.
Weiser
M R
MR
Department of Surgery, The Harvard Medical School, Boston 02115-0001, USA.
Pechet
T T
TT
Williams
J P
JP
Ma
M
M
Frenette
P S
PS
Moore
F D
FD
Kobzik
L
L
Hines
R O
RO
Wagner
D D
DD
Carroll
M C
MC
Hechtman
H B
HB
D000818:Animals; D003176:Complement C3 / Q000378:metabolism; D003169:Complement Inactivator Proteins / Q000494:pharmacology; D003170:Complement Pathway, Alternative / Q000187:drug effects / Q000502:physiology*; D003171:Complement Pathway, Classical / Q000187:drug effects / Q000502:physiology; D019040:E-Selectin / Q000502:physiology; D007124:Immunoenzyme Techniques; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D019007:P-Selectin / Q000502:physiology; D011015:Pneumonia, Aspiration / Q000473:pathology / Q000503:physiopathology*; D011650:Pulmonary Alveoli / Q000473:pathology
D003176:Complement C3; D003169:Complement Inactivator Proteins; D019040:E-Selectin; D019007:P-Selectin