4.6 Article

Platelets inhibit apoptotic lung epithelial cell death and protect mice against infection-induced lung injury

Journal

BLOOD ADVANCES
Volume 3, Issue 3, Pages 432-445

Publisher

AMER SOC HEMATOLOGY
DOI: 10.1182/bloodadvances.2018026286

Keywords

-

Categories

Funding

  1. National Heart, Lung, and Blood Institute, National Institutes of Health [4T32 HL007563, F32 HL142172, P01HL114453, R01 HL136143, HL086884, HL142084]
  2. American Heart Association [18PRE33960033]
  3. Cystic Fibrosis Foundation Research Development Program
  4. Vascular Medicine Institute
  5. Hemophilia Center of Western Pennsylvania
  6. Institute for Transfusion Medicine

Ask authors/readers for more resources

Thrombocytopenia is associated with worse outcomes in patients with acute respiratory distress syndrome, which is most commonly caused by infection and marked by alveolar-capillary barrier disruption. However, the mechanisms by which platelets protect the lung alveolar-capillary barrier during infectious injury remain unclear. We found that natively thrombocytopenic Mpl(-/-) mice deficient in the thrombopoietin receptor sustain severe lung injury marked by alveolar barrier disruption and hemorrhagic pneumonia with early mortality following acute intrapulmonary Pseudomonas aeruginosa (PA) infection; barrier disruption was attenuated by platelet reconstitution. Although PA infection was associated with a brisk neutrophil influx, depletion of airspace neutrophils failed to substantially mitigate PA-triggered alveolar barrier disruption in Mpl(-/-) mice. Rather, PA cell-free supernatant was sufficient to induce lung epithelial cell apoptosis in vitro and in vivo and alveolar barrier disruption in both platelet-depleted mice and Mpl(-/-) mice in vivo. Cell-free supernatant from PA with genetic deletion of the type 2 secretion system, but not the type 3 secretion system, mitigated lung epithelial cell death in vitro and lung injury in Mpl(-/-) mice. Moreover, platelet releasates reduced poly (ADP ribose) polymerase cleavage and lung injury in Mpl(-/-) mice, and boiling of platelet releasates, but not apyrase treatment, abrogated PA supernatant-induced lung epithelial cell cytotoxicity in vitro. These findings indicate that while neutrophil airspace influx does not potentiate infectious lung injury in the thrombocytopenic host, platelets and their factors protect against severe pulmonary complications from pathogen-secreted virulence factors that promote host cell death even in the absence of overt infection.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available