Regulators of macrophage activation

Eur J Immunol. 2011 Jun;41(6):1531-4. doi: 10.1002/eji.201141670. Epub 2011 May 24.


Macrophages are ubiquitous phagocytes that can constitute up to 15% of the cellular content of tissues. These heterogeneous cells of the innate immune system perform important functions during health and disease. Equipped with receptors for the T helper cell cytokines INF-γ and IL-4, macrophages undergo specific activation programs during Th1 or Th2 immune responses. These activation profiles, termed classical (M1) or alternative (M2) activation respectively, are further tuned by the presence and recognition of microbial-associated molecular patterns, other cytokines, lipids, and even adhesion to the substratum. The activation of macrophages also relies on the maturation background of the cells, elicitation of complicated intracellular signalling cascades, and the crosstalk between the different signalling elements. Of interest, not all genes participating in the activation-related signalling cascades are equally important for the elicitation of functional profiles and a regulator gene hierarchy is emerging for the different types of activation. In this issue of the European Journal of Immunology, two papers add to our understanding of how cellular kinases and phosphatases, related to the PI3K pathway, regulate M1 or M2 activation programmes in macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation / immunology
  • Inositol Polyphosphate 5-Phosphatases
  • MAP Kinase Kinase Kinases / genetics
  • MAP Kinase Kinase Kinases / immunology
  • MAP Kinase Kinase Kinases / metabolism*
  • Macrophage Activation / genetics*
  • Macrophages / immunology*
  • Mice
  • Mice, Knockout
  • Nitric Oxide Synthase Type II / immunology
  • Phosphatidylinositol 3-Kinases / immunology*
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / immunology
  • Phosphoric Monoester Hydrolases / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / immunology
  • Proto-Oncogene Proteins / metabolism*
  • Signal Transduction
  • Th1-Th2 Balance


  • Proto-Oncogene Proteins
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Phosphatidylinositol 3-Kinases
  • MAP Kinase Kinase Kinases
  • Map3k8 protein, mouse
  • Phosphoric Monoester Hydrolases
  • Inositol Polyphosphate 5-Phosphatases