Endothelial cell PTP1B regulates leukocyte recruitment during allergic inflammation

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20 Scopus citations


Pulmonary eosinophilia is a consistent hallmark of allergic lung inflammation. Infiltration of eosinophils into ovalbumin (OVA)-challenged lungs is dependent on the adhesion molecule vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells. Ligation of VCAM-1 activates endothelial cell protein tyrosine phosphatase 1B (PTP1B), which is required for VCAM- 1-dependent leukocyte migration in vitro. To examine whether nonhematopoietic PTP1B modulates eosinophil recruitment in vivo, mice deficient in PTP1B were irradiated and received wild-type hematopoietic cells to generate chimeric PTP1B-/- mice. In response to OVA challenge, the chimeric PTP1B-/- mice had reduced eosinophilia in the lung tissue and bronchoalveolar lavage, indicating a role for PTP1B in nonhematopoietic cells during leukocyte recruitment. To determine whether endothelial cell PTP1B modulates eosinophil recruitment, mice with an inducible endothelial cell-specific PTP1B deletion (iePTP1B mice) were generated and the PTP1B deletion was induced after antigen sensitization before antigen challenge. In response to OVA challenge, the iePTP1B mice with the endothelial cell PTP1B deletion had an increased accumulation of eosinophils bound to the luminal surface of the endothelium in the lung vasculature and had a decrease in leukocyte recruitment into the lung tissue. In the iePTP1B mice, expression of adhesion molecules, cytokines, or chemokines that regulate leukocyte recruitment during inflammation was not altered, consistent with other studies that deletion of endothelial adhesion molecule signals does not alter lung cytokines and chemokines. In summary, these data suggest that VCAM-1 activation of PTP1B in the endothelium is necessary for eosinophil recruitment during allergic inflammation. Moreover, these studies provide a basis for targeting VCAM-1-dependent signaling pathways in allergy therapies.

Original languageEnglish (US)
Pages (from-to)L240-L249
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number4
StatePublished - Feb 15 2013


  • Allergic inflammation
  • Endothelial
  • Leukocyte extravasation
  • Lung
  • PTP1B

ASJC Scopus subject areas

  • Physiology (medical)
  • Physiology
  • Pulmonary and Respiratory Medicine
  • Cell Biology


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