Cellular and Molecular Life Sciences CMLS

, Volume 60, Issue 11, pp 2334–2346

Regulation of macrophage activation

Authors

  • J. Ma
    • Department of Anatomy, Institute of BiomedicineUniversity of Helsinki
  • T. Chen
    • Department of Medicine/invärtes medicinHelsinki University Central Hospital
  • J. Mandelin
    • Department of Anatomy, Institute of BiomedicineUniversity of Helsinki
  • A. Ceponis
    • Johnson and Johnson Pharmaceutical Research and DevelopmentLaboratory of Immunology
  • N. E. Miller
    • OmniViz, Inc.
  • M. Hukkanen
    • Department of Anatomy, Institute of BiomedicineUniversity of Helsinki
  • G. F. Ma
    • Department of Anatomy, Institute of BiomedicineUniversity of Helsinki
    • Department of Medicine/invärtes medicinHelsinki University Central Hospital
    • ORTON Orthopaedic Hospital of the Invalid Foundation
    • Biomedicum
Review

DOI: 10.1007/s00018-003-3020-0

Cite this article as:
Ma, J., Chen, T., Mandelin, J. et al. CMLS, Cell. Mol. Life Sci. (2003) 60: 2334. doi:10.1007/s00018-003-3020-0

Abstract

IFN-γ rapidly primes the macrophage via JAK1/2-STAT1 pathway so that it can subsequently undergo a slower classical type 1 activation upon exposure to T helper (Th)1 cytokines such as IFNγ or other activators, including tumor necrosis factor and lipopolysaccharide, e.g. in intracellular killing of phagocytosed Mycobacterium tuberculosis. If instead it is driven by Th2 cytokines interleukin (IL)-4 and IL-13, it undergoes alternate type 2 activation, which enhances endocytotic antigen uptake and presentation, mast cell and eosinophil involvement and type 2 granuloma formation, e.g. in response to parasitic and extracellular pathogens. Particle-induced macrophage activation was shown to differ from classical and alternate activation, showing in DNA microarray experiments (complete linkage/ Euclidean distance metric analysis) upregulation of nonsecreted structural/signaling molecules and lack of secreted proin-flammatory cyto- and chemokines. The switch-off (deactivation) of already activated macrophages is an active, controlled process in which IL-10 and corticosteroids play important roles and to which15dPGJ2, PGA1/2 and vasoactive intestinal peptide often contribute.

Macrophage classical activation alternate activation priming deactivation

Copyright information

© Birkhäuser-Verlag Basel 2003