The disabled dendritic cell

FASEB J. 2001 Apr;15(6):1054-61. doi: 10.1096/fj.00-0508hyp.

Abstract

Dendritic cells are important antigen-presenting cells of the immune system that induce and modulate immune responses. They interact with T and B lymphocytes as well as with natural killer cells to promote activation and differentiation of these cells. Dendritic cells generated in vitro from monocytes by use of the cytokines GM-CSF and IL-4 are increasingly used clinically to enhance antitumor immunity in cancer patients. However, recent studies revealed that the functional repertoire of monocyte-derived dendritic cells may be incomplete. Important functions of monocyte-derived dendritic cells such as migration or the ability to induce natural killer cell activation or type 2 T helper cell differentiation appear to be impaired. We propose that all these deficiencies relate to a single biochemical deficiency of monocyte-derived dendritic cells. IL-4, which is used to generate monocyte-derived dendritic cells, suppresses phospholipase A2, the enzyme that liberates arachidonic acid from membrane phospholipids and contributes to the synthesis of platelet-activating factor. Monocyte-derived dendritic cells must therefore fail to generate platelet-activating factor as well as arachidonic acid derivatives such as prostaglandins, leukotrienes, and lipoxins, collectively referred to as eicosanoids. Since eicosanoids and platelet-activating factor are known to play an important role in processes such as leukocyte migration, natural killer cell activation, and type 2 T helper cell differentiation, the deficiency in eicosanoid and platelet-activating factor biosynthesis may be responsible for the observed handicaps of monocyte-derived dendritic cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen-Presenting Cells / cytology
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Arachidonic Acid / metabolism*
  • B-Lymphocytes / immunology
  • Cell Differentiation / immunology*
  • Cell Movement / physiology
  • Cells, Cultured
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Humans
  • Killer Cells, Natural / immunology
  • Lymphocyte Activation / immunology*

Substances

  • Arachidonic Acid