Endothelial microparticles induce inflammation in acute lung injury.
BACKGROUND
Previously, we have shown that endothelial microparticles (EMPs) injected into mice induce acute lung injury (ALI) [1]. In this study, we hypothesize that EMPs induce ALI by initiating cytokine release in the lung, leading to recruitment and activation of neutrophils.


METHODS
C57BL/6J male mice (8-10 wk old) were intravenously injected with EMPs (200,000/mL), LPS (2 mg/kg), or both. Bronchoalveolar lavage (BAL) and serum levels of IL-1β and TNF-α were analyzed by enzyme-linked immunoassay (ELISA). Morphometric analysis was performed on H and E stained lung sections. Myeloperoxidase (MPO) levels were determined via an enzymatic assay and immunofluorescence of stained sections.


RESULTS
EMPs led to significantly increased pulmonary and systemic IL-1β and TNF-α levels, which correlated with increased neutrophil recruitment to the lung. MPO levels in the lungs were increased significantly following injection of EMPs or LPS, compared to PBS. In mice treated with EMPs and LPS either simultaneously or successively, the cytokine and MPO levels were significantly increased over that of either treatment alone.


CONCLUSIONS
EMPs contribute to lung injury through the initiation of a cytokine cascade that increases recruitment of neutrophils and subsequent release of MPO. Furthermore, treatment of mice with both EMPs and LPS induced greater lung injury than either treatment alone, suggesting that EMPs prime the lung for increased injury by other pathogens. Therapies aimed at reducing or blocking EMPs may be a useful strategy for attenuating lung injury.
Buesing
Keely L
KL
Children's Research Institute, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Densmore
John C
JC
Kaul
Sushma
S
Pritchard
Kirkwood A
KA
Jarzembowski
Jason A
JA
Gourlay
David M
DM
Oldham
Keith T
KT
D055371:Acute Lung Injury / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D055252:Cell-Derived Microparticles / Q000276:immunology* / Q000473:pathology; D042783:Endothelial Cells / Q000276:immunology* / Q000473:pathology; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014471:Umbilical Veins / Q000166:cytology
D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase