Endothelial signaling by neutrophil-released oncostatin M enhances P-selectin-dependent inflammation and thrombosis

Blood Adv. 2019 Jan 22;3(2):168-183. doi: 10.1182/bloodadvances.2018026294.


In the earliest phase of inflammation, histamine and other agonists rapidly mobilize P-selectin to the apical membranes of endothelial cells, where it initiates rolling adhesion of flowing neutrophils. Clustering of P-selectin in clathrin-coated pits facilitates rolling. Inflammatory cytokines typically signal by regulating gene transcription over a period of hours. We found that neutrophils rolling on P-selectin secreted the cytokine oncostatin M (OSM). The released OSM triggered signals through glycoprotein 130 (gp130)-containing receptors on endothelial cells that, within minutes, further clustered P-selectin and markedly enhanced its adhesive function. Antibodies to OSM or gp130, deletion of the gene encoding OSM in hematopoietic cells, or conditional deletion of the gene encoding gp130 in endothelial cells inhibited neutrophil rolling on P-selectin in trauma-stimulated venules of the mouse cremaster muscle. In a mouse model of P-selectin-dependent deep vein thrombosis, deletion of OSM in hematopoietic cells or of gp130 in endothelial cells markedly inhibited adhesion of neutrophils and monocytes and the rate and extent of thrombus formation. Our results reveal a paracrine-signaling mechanism by which neutrophil-released OSM rapidly influences endothelial cell function during physiological and pathological inflammation.

Publication types

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

MeSH terms

  • Animals
  • Biomarkers
  • Cell Adhesion
  • Cell Communication
  • Clathrin-Coated Vesicles / metabolism
  • Cytokine Receptor gp130 / metabolism
  • Disease Models, Animal
  • Disease Susceptibility
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / metabolism*
  • Humans
  • Immunophenotyping
  • Leukocyte Rolling
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Neutrophils / immunology
  • Neutrophils / metabolism*
  • Oncostatin M / metabolism*
  • P-Selectin / genetics
  • P-Selectin / metabolism*
  • Protein Binding
  • Signal Transduction
  • Thrombosis / etiology*
  • Thrombosis / metabolism*
  • Thrombosis / pathology
  • Vasculitis / etiology*
  • Vasculitis / metabolism*
  • Vasculitis / pathology


  • Biomarkers
  • IL6ST protein, human
  • P-Selectin
  • Oncostatin M
  • Cytokine Receptor gp130