title: Complement 3 is involved with ventilator-induced lung injury.
abstract: Humoral molecules can trigger injury on mechanically stressed and damaged tissue. We have studied the role of complement 3 (C3) in a mouse model of ventilator-induced lung injury (VILI). Compared with sham-treated wild type (WT) mice, ventilated WT mice have reduced total bronchoalveolar lavage (BAL) cells; and elevated activities of thrombin and matrix metalloproteinases (MMPs), such as gelatinase/collagenase in the BAL fluid. In contrast, these parameters in ventilated C3 null mice are not significantly different from sham-treated WT and C3 null mice. In mechanically ventilated mice, thrombin activity and MMPs are lower in C3 null mice than in WT mice and are inversely correlated with total single BAL cells. C3 activation is associated with MMP activation in vitro. Pretreatment of WT mice with humanized cobra venom factor, which inactivates C3, reduces C3 deposition in the lung and increases total BAL cells in VILI. We propose that C3 is involved with VILI and inhibition of complement activation may be a potential therapeutic strategy.
authors: Program of Developmental Immunology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. ktakahashi1@partners.org
authors: Kazue
authors: K
authors: Takahashi
authors: Dalia
authors: D
authors: Saha
authors: Ivany
authors: I
authors: Shattino
authors: Vasile I
authors: VI
authors: Pavlov
authors: Gregory L
authors: GL
authors: Stahl
authors: Paul
authors: P
authors: Finnegan
authors: Marcos F Vidal
authors: MF
authors: Melo
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003167:Complement Activation; D003176:Complement C3 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D020782:Matrix Metalloproteinases / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D010586:Phagocytes / Q000166:cytology / Q000378:metabolism; D013917:Thrombin / Q000032:analysis; D055397:Ventilator-Induced Lung Injury / Q000276:immunology*
chemical_list: D003176:Complement C3; D013917:Thrombin; D020782:Matrix Metalloproteinases