Endothelial microparticles induce inflammation in acute lung injury. J Surg Res 2011 Mar;166(1):32-9
Date
09/11/2010Pubmed ID
20828748Pubmed Central ID
PMC4731030DOI
10.1016/j.jss.2010.05.036Scopus ID
2-s2.0-79951678163 (requires institutional sign-in at Scopus site) 80 CitationsAbstract
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.
MATERIALS AND 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.
CONCLUSION: 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.
Author List
Buesing KL, Densmore JC, Kaul S, Pritchard KA Jr, Jarzembowski JA, Gourlay DM, Oldham KTAuthors
John C. Densmore MD Professor in the Surgery department at Medical College of WisconsinDavid M. Gourlay MD Chief, Professor in the Surgery department at Medical College of Wisconsin
Jason A. Jarzembowski MD, PhD Sr Associate Dean, CEO CSG, Professor in the Pathology department at Medical College of Wisconsin
Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Acute Lung InjuryAnimals
Bronchoalveolar Lavage Fluid
Cell-Derived Microparticles
Endothelial Cells
Humans
Interleukin-1beta
Male
Mice
Mice, Inbred C57BL
Neutrophils
Peroxidase
Pneumonia
Tumor Necrosis Factor-alpha
Umbilical Veins
