C5a and TNF-alpha up-regulate the expression of tissue factor in intra-alveolar neutrophils of patients with the acute respiratory distress syndrome

Konstantinos Kambas, Maciej M Markiewski, Ioannis A Pneumatikos, Stavros S Rafail, Vassiliki Theodorou, Dimitrios Konstantonis, Ioannis Kourtzelis, Michael N Doumas, Paola Magotti, Robert A Deangelis, John D Lambris, Konstantinos D Ritis

Research output: Contribution to journalArticlepeer-review


Acute respiratory distress syndrome (ARDS) is characterized by the presence of fibrin-rich inflammatory exudates in the intra-alveolar spaces and the extensive migration of neutrophils into alveoli of the lungs. Tissue factor (TF)-dependent procoagulant properties of bronchoalveaolar lavage fluid (BALF) obtained from ARDS patients favor fibrin deposition, and are likely the result of cross-talk between inflammatory mediators and hemostatic mechanisms. However, the regulation of these interactions remains elusive. Prompted by previous findings suggesting that neutrophils, under certain inflammatory conditions, can express functional TF, we investigated the contribution of intra-alveolar neutrophils to the procoagulant properties of BALF from patients with ARDS. Our results confirm that the procoagulant properties of BALF from ARDS patients are the result of TF induction, and further indicate that BALF neutrophils are a main source of TF in intra-alveolar fluid. We also found that BALF neutrophils in these patients express significantly higher levels of TF than peripheral blood neutrophils. These results suggest that the alveolar microenvironment contributes to TF induction in ARDS. Additional experiments indicated that the ability of BALF to induce TF expression in neutrophils from healthy donors can be abolished by inhibiting C5a or TNF-alpha signaling, suggesting a primary role for these inflammatory mediators in the up-regulation of TF in alveolar neutrophils in ARDS. This cross-talk between inflammatory mediators and the induction of TF expression in intra-alveolar neutrophils may be a potential target for novel therapeutic strategies to limit ARDS-associated disturbances of coagulation.

Original languageEnglish
Pages (from-to)7368-75
Number of pages8
JournalJournal of Immunology
Issue number11
Publication statusPublished - 1 Jun 2008


  • Adult
  • Aged
  • Bronchoalveolar Lavage Fluid/cytology
  • Complement C5a/immunology
  • Cytokines/immunology
  • Fibrin/immunology
  • Humans
  • Middle Aged
  • Neutrophils/immunology
  • Respiratory Distress Syndrome, Adult/immunology
  • Thromboplastin/immunology
  • Tumor Necrosis Factor-alpha/immunology

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