title: Characterization of Microvesicles in Septic Shock Using High-Sensitivity Flow Cytometry.
abstract: Endothelial pathology is considered to play a key role in septic shock. Since endothelial-derived microvesicles (MV) are elevated in various diseases associated with endothelial pathology, they are considered surrogate markers of the endothelial state. By analyzing the signature of circulating MV with high-sensitivity flow cytometry (hsFC), we wanted to test the hypothesis whether endothelial-derived MV are increased in septic shock.
  
  
  
  MV in blood from healthy volunteers and patients with septic shock treated in a medical intensive care unit were quantified by hsFC, which has an improved detection limit of approximately 0.3 μm.
  
  
  
  Patients with septic shock (n = 30) showed 3-fold higher levels of CD31+/CD41- MV (58.5 (26.4-101.2) [median (25th-75th percentile)] vs. 19.5 (12.8-25.4) MV/μL; P <0.001) compared with healthy volunteers (n = 18). Absolute counts of CD144+, CD62E+, and CD106+ MV, specific for endothelial-derived MV, were low in all groups. The number of CD31+/CD41- MV correlated significantly with leukocyte count (rs = 0.64; P <0.001). Platelet-derived CD41+ MV were significantly elevated in the group dying within 48 h after inclusion (639.1 (321.3-969.7) vs. 221.5 (119.5-456.9) MV/μL; P = 0.037). Patients dying within 48 h had also significantly higher levels of CD31+/CD41-/AnnexinV- MV (51.9 (24.9-259.8) vs. 18.9 (9.7-31) MV/μL; P = 0.028).
  
  
  
  Despite an improved detection limit for MV by using hsFC, counts of endothelial-specific MV are unexpectedly low in patients with septic shock. Increased amounts of CD41+ and CD31+/CD41-/AnnexinV- MV indicate release by activated platelets and possibly leukocytes correlating with unfavorable outcome.
authors.affiliation: *Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria †Department of Internal Medicine V-Haematology and Oncology, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Georg Franz
authors.initials: GF
authors.lastname: Lehner
authors.forename: Ulrich
authors.initials: U
authors.lastname: Harler
authors.forename: Viktoria Maria
authors.initials: VM
authors.lastname: Haller
authors.forename: Clemens
authors.initials: C
authors.lastname: Feistritzer
authors.forename: Julia
authors.initials: J
authors.lastname: Hasslacher
authors.forename: Stefan
authors.initials: S
authors.lastname: Dunzendorfer
authors.forename: Romuald
authors.initials: R
authors.lastname: Bellmann
authors.forename: Michael
authors.initials: M
authors.lastname: Joannidis
mesh_terms: D000328:Adult; D000368:Aged; D017304:Annexin A5 / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D040201:Platelet Membrane Glycoprotein IIb / Q000378:metabolism; D012772:Shock, Septic / Q000097:blood / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D055815:Young Adult; D000099152:Cadherin 5
chemical_list: D017304:Annexin A5; D015703:Antigens, CD; D015820:Cadherins; D019040:E-Selectin; D016753:Interleukin-10; D015850:Interleukin-6; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D040201:Platelet Membrane Glycoprotein IIb; D019010:Vascular Cell Adhesion Molecule-1; D000099152:Cadherin 5