Human monocytes but not dendritic cells are killed by blocking of autocrine cyclooxygenase activity

Cell Immunol. 2009;258(1):107-14. doi: 10.1016/j.cellimm.2009.03.019. Epub 2009 Apr 25.

Abstract

Dendritic cells (DCs), in peripheral tissues, derive mostly from blood precursors that differentiate into DCs under the influence of the local microenvironment. Monocytes constitute the main known DC precursors in blood and their infiltration into tissues is up-regulated during inflammation. During this process, the local production of mediators, like prostaglandins (PGs), influence significantly DC differentiation and function. In the present paper we show that treatment of blood adherent mononuclear cells with 10microM indomethacin, a dose achieved in human therapeutic settings, causes monocytes' progressive death but does not affect DCs viability or cell surface phenotype. This resistance of DCs was observed both for cells differentiated in vitro from blood monocytes and for a population with DCs characteristics already present in blood. This phenomenon could affect the local balance of antigen-presenting cells, influence the induction and pattern of immune responses developed under the treatment with non-steroidal anti-inflammatory drugs and, therefore, deserves further investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cell Death
  • Cell Differentiation / drug effects
  • Cell Survival / drug effects
  • Cyclooxygenase Inhibitors / pharmacology*
  • Dendritic Cells / drug effects*
  • Dendritic Cells / enzymology
  • Dendritic Cells / immunology
  • Humans
  • Indomethacin / pharmacology*
  • Monocytes / drug effects*
  • Monocytes / enzymology
  • Monocytes / immunology
  • Prostaglandin-Endoperoxide Synthases / drug effects*
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Tumor Necrosis Factor-alpha
  • Prostaglandin-Endoperoxide Synthases
  • Indomethacin