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2011 ; 45
(4
): 834-42
Nephropedia Template TP
Sun S
; Wang H
; Zhao G
; An Y
; Guo Y
; Du L
; Song H
; Qiao F
; Yu H
; Wu X
; Atkinson C
; Jiang S
; Tomlinson S
; Zhou Y
Am J Respir Cell Mol Biol
2011[Oct]; 45
(4
): 834-42
PMID21421909
show ga
The widely used herbicide, paraquat (PQ), is highly toxic and claims thousands of
lives from both accidental and voluntary ingestion. The pathological mechanisms
of PQ poisoning-induced acute lung injury (ALI) are not well understood, and the
role of complement in PQ-induced ALI has not been elucidated. We developed and
characterized a mouse model of PQ-induced ALI and studied the role of complement
in the pathogenesis of PQ poisoning. Intraperitoneal administration of PQ caused
dose- and time-dependent lung damage and mortality, with associated inflammatory
response. Within 24 hours of PQ-induced ALI, there was significantly increased
expression of the complement proteins, C1q and C3, in the lung. Expression of the
anaphylatoxin receptors, C3aR and C5aR, was also increased. Compared with
wild-type mice, C3-deficient mice survived significantly longer and displayed
significantly reduced lung inflammation and pathology after PQ treatment. Similar
reductions in PQ-induced inflammation, pathology, and mortality were recorded in
mice treated with the C3 inhibitors, CR2-Crry, and alternative pathway specific
CR2-fH. A similar therapeutic effect was also observed by treatment with either
C3a receptor antagonist or a blocking C5a receptor monoclonal antibody. Together,
these studies indicate that PQ-induced ALI is mediated through receptor signaling
by the C3a and C5a complement activation products that are generated via the
alternative complement pathway, and that complement inhibition may be an
effective clinical intervention for postexposure treatment of PQ-induced ALI.
|*Paraquat
[MESH]
|Acute Lung Injury/chemically induced/genetics/immunology/pathology/*prevention &
control
[MESH]
free
free
free
