Platelet activation contributes to hypoxia-induced inflammation

Am J Physiol Lung Cell Mol Physiol. 2021 Mar 1;320(3):L413-L421. doi: 10.1152/ajplung.00519.2020. Epub 2020 Dec 2.


Inflammation is central to the pathogenesis of pulmonary vascular remodeling and pulmonary hypertension (PH). Inflammation precedes remodeling in preclinical models, thus supporting the concept that changes in immunity drive remodeling in PH. Platelets are recognized as mediators of inflammation, but whether platelets contribute to hypoxia-driven inflammation has not been studied. We utilized a murine hypoxia model to test the hypothesis that platelets drive hypoxia-induced inflammation. We evaluated male and female 9-wk-old normoxic and hypoxic mice and in selected experiments included hypoxic thrombocytopenic mice. Thrombocytopenic mice were generated with an anti-GP1bα rat IgG antibody. We also performed immunostaining of lung sections from failed donor controls and patients with idiopathic pulmonary arterial hypertension. We found that platelets are increased in the lungs of hypoxic mice and hypoxia induces platelet activation. Platelet depletion prevents hypoxia-driven increases in the proinflammatory chemokines CXCL4 and CCL5 and attenuates hypoxia-induced increase in plasma CSF-2. Pulmonary interstitial macrophages are increased in the lungs of hypoxic mice; this increase is prevented in thrombocytopenic mice. To determine the potential relevance to human disease, lung sections from donors and patients with advanced idiopathic pulmonary arterial hypertension (iPAH) were immunostained for the platelet-specific protein CD41. We observed iPAH lungs had a two-fold increase in CD41, compared with controls. Our data provide evidence that the platelet count is increased in the lungs and activated in mice with hypoxia-induced inflammation and provides rationale for the further study of the potential contribution of platelets to inflammatory mediated vascular remodeling and PH.

Keywords: hypertension; hypoxia; inflammation; platelet; pulmonary hypertension.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blood Platelets / immunology*
  • Blood Platelets / pathology
  • Chemokine CCL5 / immunology
  • Disease Models, Animal
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Hypoxia / immunology*
  • Hypoxia / pathology
  • Inflammation / immunology
  • Inflammation / pathology
  • Lung / immunology*
  • Lung / pathology
  • Male
  • Mice
  • Platelet Activation / immunology*
  • Platelet Factor 4 / immunology
  • Pneumonia / immunology*
  • Pneumonia / pathology
  • Thrombocytopenia / chemically induced
  • Thrombocytopenia / immunology
  • Thrombocytopenia / pathology


  • Ccl5 protein, mouse
  • Chemokine CCL5
  • Platelet Factor 4
  • Granulocyte-Macrophage Colony-Stimulating Factor