Maresin 1 mitigates LPS-induced acute lung injury in mice.
OBJECTIVE
Acute lung injury (ALI) is a severe illness with a high rate of mortality. Maresin 1 (MaR1) was recently reported to regulate inflammatory responses. We used a LPS-induced ALI model to determine whether MaR1 can mitigate lung injury.


METHODS
Male BALB/c mice were injected, intratracheally, with either LPS (3 mg·kg(-1) ) or normal saline (1.5 mL·kg(-1) ). After this, normal saline, a low dose of MaR1 (0.1 ng per mouse) or a high dose of MaR1 (1 ng per mouse) was given i.v. Lung injury was evaluated by detecting arterial blood gas, pathohistological examination, pulmonary oedema, inflammatory cell infiltration, inflammatory cytokines in the bronchoalveolar lavage fluid and neutrophil-platelet interactions.


RESULTS
The high dose of MaR1 significantly inhibited LPS-induced ALI by restoring oxygenation, attenuating pulmonary oedema and mitigating pathohistological changes. A combination of elisa and immunohistochemistry showed that high-dose MaR1 attenuated LPS-induced increases in pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), chemokines [keratinocyte chemokine, monocyte chemoattractant protein-5, macrophage inflammatory protein (MIP)-1α and MIP-1γ], pulmonary myeloperoxidase activity and neutrophil infiltration in the lung tissues. Consistent with these observations, flow cytometry and Western blotting indicated that MaR1 down-regulated LPS-induced neutrophil adhesions and suppressed the expression of intercellular adhesion molecule (ICAM)-1, P-selection and CD24.


CONCLUSIONS
High-dose MaR1 mitigated LPS-induced lung injury in mice by inhibiting neutrophil adhesions and decreasing the levels of pro-inflammatory cytokines.
Department of Critical Care Medicine, Institute of Anesthesia and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Jie
J
Gong
Zhou-yang
ZY
Wu
Hong
H
Qi
Lin
L
Chen
Hong-bin
HB
Li
Bo
B
Li
Cheng-ye
CY
Yao
Ya-xin
YX
Wang
Jing
J
Wu
Shi-ying
SY
Yuan
Shang-long
SL
Yao
You
Y
Shang
D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D000280:Administration, Inhalation; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology
C535211:7,14-dihydroxydocosa-4,8,10,12,16,19-hexaenoic acid; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D004281:Docosahexaenoic Acids
Maresin 1; acute lung injury; lipopolysaccharide; neutrophils; platelets; resolution