Human and murine high endothelial venule cells phagocytose apoptotic leukocytes

Krista L. Hess, Kim Sue R S Tudor, Jacob D. Johnson, Farzaneh Osati-Ashtiani, David S. Askew, Joan M. Cook-Mills*

*Corresponding author for this work

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Apoptotic cell death occurs during normal lymphocyte development and differentiation as well as following lymphocyte exposure to endogenous corticosteroids released during stress, malnutrition, and trauma. Recognition and engulfment of these apoptotic cells is important for the clearance of dying cells before they release potent inflammatory mediators into the vasculature or tissues. Phagocytosis of apoptotic cells is accomplished in part by macrophages. We report for the first time that apoptotic lymphocytes are also phagocytosed by high endothelial venule (HEV) cells. The murine HEV cell line mHEVa rapidly phagocytosed apoptotic lymphoid and myeloid cells with the greatest rate of phagocytosis occurring at 06 h. To confirm HEV cell interaction with apoptotic cells, we demonstrated that apoptotic human tonsil lymphocytes were phagocytosed by human tonsil HEV cells in primary cultures. Furthermore, we examined HEV cell phagocytosis in vivo. Mice were treated with a natural corticosterone (4-pregnene-11β,21-diol-3,20-dione) at levels detected during stress or malnutrition (93-180 μg serum cortisol/dl). At 4- 12 h posttreatment, apoptotic lymphocytes were present inside vacuoles of HEV cells in axillary lymph node tissue sections, as determined by transmission electron microscopy. These data suggest that, in addition to macrophages, lymph node HEV cells also play a role in the removal of apoptotic lymphocytes. Moreover, since HEV cells are specialized endothelial cells that regulate lymphocyte migration into peripheral lymphoid tissues, they may provide an important checkpoint for clearance of apoptotic lymphocytes within the vasculature, as well as limiting entrance of nonfunctional lymphocytes into the lymph node.

Original languageEnglish (US)
Pages (from-to)404-411
Number of pages8
JournalExperimental Cell Research
Volume236
Issue number2
DOIs
StatePublished - Nov 1 1997

Keywords

  • Apoptosis
  • Endothelial cells
  • Human
  • Lymph node
  • Mouse
  • Phagocytosis
  • Tonsil

ASJC Scopus subject areas

  • Cell Biology

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