title: Gram-Negative Pneumonia Alters Large-Vein Cell-Adhesion Molecule Profile and Potentiates Experimental Stasis Venous Thrombosis.
abstract: OBJECTIVE
  Pneumonia is a significant risk factor for the development of venous thrombosis (VT). Cell-adhesion molecules (CAMs) are linked to the pathogenesis of both pneumonia and VT. We hypothesized that remote infection would confer a prothrombogenic milieu via systemic elevation of CAMs.
  
  
  METHODS
  Lung injury was induced in wild-type (C57BL/6) mice by lung contusion or intratracheal inoculation with Klebsiella pneumoniae or saline controls. K. pneumoniae-treated mice and controls additionally underwent inferior vena cava (IVC) ligation to generate VT.
  
  
  RESULTS
  Lung-contusion mice demonstrated no increase in E-selectin or P-selectin whereas mice infected with K. pneumoniae demonstrated increased circulating P-selectin, ICAM-1, VCAM-1 and thrombin-antithrombin (TAT) complexes. Mice with pneumonia formed VT 3 times larger than controls, demonstrated significantly more upregulation of vein-wall and systemic CAMs, and formed erythrocyte-rich thrombi.
  
  
  CONCLUSIONS
  Elevated CAM expression was identified in mice with pneumonia, but not lung contusion, indicating that the type of inflammatory stimulus and the presence of infection drive the vein-wall response. Elevation of CAMs was associated with amplified VT and may represent an alternate mechanism by which to target the prevention of VT.
authors: Conrad Jobst Vascular Research Laboratory, University of Michigan Medical School, Ann Arbor, Mich., USA.
authors: Andrea T
authors: AT
authors: Obi
authors: Elizabeth
authors: E
authors: Andraska
authors: Yogendra
authors: Y
authors: Kanthi
authors: Catherine E
authors: CE
authors: Luke
authors: Megan
authors: M
authors: Elfline
authors: Suresh
authors: S
authors: Madathilparambil
authors: Teruna J
authors: TJ
authors: Siahaan
authors: Farouc A
authors: FA
authors: Jaffer
authors: Thomas W
authors: TW
authors: Wakefield
authors: Krishnan
authors: K
authors: Raghavendran
authors: Peter K
authors: PK
authors: Henke
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000150:complications; D000818:Animals; D000990:Antithrombin III; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000097:blood*; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D007710:Klebsiella Infections / Q000097:blood / Q000150:complications* / Q000188:drug therapy / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000472:pathogenicity*; D008026:Ligation; D008297:Male; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000097:blood; D010447:Peptide Hydrolases / Q000097:blood; D018410:Pneumonia, Bacterial / Q000097:blood / Q000150:complications* / Q000188:drug therapy / Q000382:microbiology; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014682:Vena Cava, Inferior / Q000378:metabolism* / Q000601:surgery; D020246:Venous Thrombosis / Q000097:blood / Q000209:etiology* / Q000382:microbiology / Q000517:prevention & control
chemical_list: D015815:Cell Adhesion Molecules; D005343:Fibrinolytic Agents; C090509:Icam1 protein, mouse; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1; C046193:antithrombin III-protease complex; D018799:Intercellular Adhesion Molecule-1; D000990:Antithrombin III; D010447:Peptide Hydrolases