Procoagulant alveolar microparticles in the lungs of patients with acute respiratory distress syndrome.
Coagulation and fibrinolysis abnormalities are observed in acute lung injury (ALI) in both human disease and animal models and may contribute to ongoing inflammation in the lung. Tissue factor (TF), the main initiator of the coagulation cascade, is upregulated in the lungs of patients with ALI/acute respiratory distress syndrome (ARDS) and likely contributes to fibrin deposition in the air space. The mechanisms that govern TF upregulation and activation in the lung are not well understood. In the vascular space, TF-bearing microparticles (MPs) are central to clot formation and propagation. We hypothesized that TF-bearing MPs in the lungs of patients with ARDS contribute to the procoagulant phenotype in the air space during acute injury and that the alveolar epithelium is one potential source of TF MPs. We studied pulmonary edema fluid collected from patients with ARDS compared with a control group of patients with hydrostatic pulmonary edema. Patients with ARDS have higher concentrations of MPs in the lung compared with patients with hydrostatic edema (25.5 IQR 21.3-46.9 vs. 7.8 IQR 2.3-27.5 micromol/l, P = 0.009 by Mann-Whitney U-test). These MPs are enriched for TF, have procoagulant activity, and likely originate from the alveolar epithelium [as measured by elevated levels of RAGE (receptor for advanced glycation end products) in ARDS MPs compared with hydrostatic MPs]. Furthermore, alveolar epithelial cells in culture release procoagulant TF MPs in response to a proinflammatory stimulus. These findings suggest that alveolar epithelial-derived MPs are one potential source of TF procoagulant activity in the air space in ARDS and that epithelial MP formation and release may represent a unique therapeutic target in ARDS.
Bastarache
Julie A
JA
Vanderbilt Univ. School of Medicine, Nashville, TN 37232-2650, USA. julie.bastarache@vanderbilt.edu
Fremont
Richard D
RD
Kropski
Jonathan A
JA
Bossert
Frederick R
FR
Ware
Lorraine B
LB
D000328:Adult; D000368:Aged; D001779:Blood Coagulation Factors / Q000378:metabolism*; D001826:Body Fluids / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000378:metabolism* / Q000648:ultrastructure; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D011014:Pneumonia / Q000150:complications / Q000473:pathology; D011650:Pulmonary Alveoli / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D011654:Pulmonary Edema / Q000150:complications / Q000473:pathology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000150:complications / Q000401:mortality / Q000473:pathology*; D013347:Subcellular Fractions / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism
D001779:Blood Coagulation Factors; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D013925:Thromboplastin
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