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Cited by 127Blood Coagulation and Thrombosis MechanismsRespiratory Support and MechanismsInflammation biomarkers and pathways

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C5a and TNF-α Up-Regulate the Expression of Tissue Factor in Intra-Alveolar Neutrophils of Patients with the Acute Respiratory Distress Syndrome

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Kambas, Konstantinos, Markiewski, Maciej M, Pneumatikos, Ioannis A, Rafail, Stavros S, Theodorou, Vassiliki, Konstantonis, Dimitrios, Kourtzelis, Ioannis, Doumas, Michael N, Magotti, Paola, DeAngelis, Robert A, Lambris, John D, Ritis, Konstantinos D·2008·The Journal of Immunology
DOI 10.4049/jimmunol.180.11.7368PMC PMC2673518
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Abstract

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-α 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.

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Metadata

Authors
Kambas, K., Markiewski, M. M., Pneumatikos, I. A., Rafail, S. S., Theodorou, V., Konstantonis, D., Kourtzelis, I., Doumas, M. N., Magotti, P., DeAngelis, R. A., Lambris, J. D., & Ritis, K. D.
Affiliations
  • Democritus University of Thrace (GR)
  • University of Pennsylvania (US)
Corresponding author
  • Kambas, Konstantinos
  • Kourtzelis, Ioannis
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2008-06-01
Volume
180
Issue
11
Pages
7368-7375
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.180.11.7368
PMC
PMC2673518
OpenAlex
W2132616983
Cited by
127
References
55
Citations by year
2026: 2 · 2025: 4 · 2024: 3 · 2023: 6 · 2022: 11 · 2021: 18 · 2020: 8 · 2019: 4 · 2018: 7 · 2017: 4 · 2016: 7 · 2015: 9 · 2014: 6 · 2013: 8 · 2012: 4
FWCI
5.63
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (AI068730)
  • National Institute of General Medical Sciences (GM-62134, R01GM062134)
  • National Institute of Allergy and Infectious Diseases (AI 068730, P01AI068730)
Topics
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
Keywords
acute respiratory distress syndrome, tissue factor, neutrophils, C5a, TNF-α, procoagulant activity, bronchoalveolar lavage fluid, fibrin deposition, alveolitis, coagulation, complement signaling, inflammatory mediators
MeSH terms
Adult, Aged, Bronchoalveolar Lavage Fluid, Fibrin, Humans, Middle Aged, Neutrophils, Respiratory Distress Syndrome, Thromboplastin, Tumor Necrosis Factor-alpha, Complement C5a, Cytokines

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