Serpine2 deficiency results in lung lymphocyte accumulation and bronchus-associated lymphoid tissue formation

Academic Article

Abstract

  • © FASEB. Serine proteinase inhibitor, clade E, member 2 (SERPINE2), is a cell- and extracellular matrix-associated inhibitor of thrombin. Although SERPINE2 is a candidate susceptibility gene for chronic obstructive pulmonary disease, the physiologic role of this protease inhibitor in lung development and homeostasis is unknown. We observed spontaneous monocytic-cell infiltration in the lungs of Serpine2-deficient (SE2-/-) mice, beginning at or before the time of lung maturity, which resulted in lesions that resembled bronchus-associated lymphoid tissue (BALT). The initiation of lymphocyte accumulation in the lungs of SE2-/- mice involved the excessive expression of chemokines, cytokines, and adhesion molecules that are essential for BALT induction, organization, and maintenance. BALT-like lesion formation in the lungs of SE2-/- mice was also associated with a significant increase in the activation of thrombin, a recognized target of SE2, and excess stimulation of NF-κB, a major regulator of chemokine expression and inflammation. Finally, systemic delivery of thrombin rapidly stimulated lung chemokine expression in vivo. These data uncover a novel mechanism whereby loss of serine protease inhibition leads to lung lymphocyte accumulation.
  • Digital Object Identifier (doi)

    Author List

  • Solleti SK; Srisuma S; Bhattacharya S; Rangel-Moreno J; Bijli KM; Randall TD; Rahman A; Mariani TJ
  • Start Page

  • 2615
  • End Page

  • 2626
  • Volume

  • 30
  • Issue

  • 7