title: Kinetics of lung tissue factor expression and procoagulant activity in bleomycin induced acute lung injury.
abstract: BACKGROUND
  Activation of coagulation by expression of tissue factor (TF) in the airspace is a hallmark of acute lung injury (ALI) but the timing of TF activation in relationship to increases in lung permeability and inflammation are unknown.
  
  
  METHODS
  To test the hypothesis that TF is upregulated early in the course of acute bleomycin lung injury and precedes increased permeability and inflammation we studied the early course of bleomycin-induced ALI in mice. Mice were treated with 0.04U intratracheal bleomycin or vehicle control and bronchoalveolar lavage (BAL) and lung tissue were collected daily for 7 days. Whole lung TF mRNA was determined by QT-PCR. TF protein was assessed by ELISA and immunostaining. BAL procoagulant activity was measured by BAL clot time and thrombin-antithrombin complexes. Inflammation was assessed by BAL cell count, differentials and CXCL1/KC concentration. Lung permeability was assessed by BAL protein and lung wet to dry weight ratio.
  
  
  RESULTS
  Expression of CXCL1 occurred by day 1. BAL protein and lung wet-to-dry weight ratio increased significantly by day 3. TF mRNA and BAL procoagulant activity peaked on day 4 while whole lung TF protein peaked on day 6. Changes in permeability and procoagulant activity preceded inflammatory cell influx which was maximal at day 6 while whole lung TF protein peaked along with inflammation.
  
  
  CONCLUSIONS
  These data demonstrate that cytokine upregulation is the earliest response to bleomycin administration, followed by increased lung permeability, upregulation of TF, and recruitment of inflammatory cells.
authors.affiliation: Division of Emergency Intensive Care Unit, the Second Hospital of Lanzhou University, Lanzhou, China, mali1105@126.com.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Ciara M
authors.initials: CM
authors.lastname: Shaver
authors.forename: Brandon S
authors.initials: BS
authors.lastname: Grove
authors.forename: Daphne B
authors.initials: DB
authors.lastname: Mitchell
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Wickersham
authors.forename: Robert H
authors.initials: RH
authors.lastname: Carnahan
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Cooper
authors.forename: Brittany E
authors.initials: BE
authors.lastname: Brake
authors.forename: Lorraine B
authors.initials: LB
authors.lastname: Ware
authors.forename: Julie A
authors.initials: JA
authors.lastname: Bastarache