Alveolar macrophages: plasticity in a tissue-specific context

Nat Rev Immunol. 2014 Feb;14(2):81-93. doi: 10.1038/nri3600. Epub 2014 Jan 21.


Alveolar macrophages exist in a unique microenvironment and, despite historical evidence showing that they are in close contact with the respiratory epithelium, have until recently been investigated in isolation. The microenvironment of the airway lumen has a considerable influence on many aspects of alveolar macrophage phenotype, function and turnover. As the lungs adapt to environmental challenges, so too do alveolar macrophages adapt to accommodate the ever-changing needs of the tissue. In this Review, we discuss the unique characteristics of alveolar macrophages, the mechanisms that drive their adaptation and the direct and indirect influences of epithelial cells on them. We also highlight how airway luminal macrophages function as sentinels of a healthy state and how they do not respond in a pro-inflammatory manner to antigens that do not disrupt lung structure. The unique tissue location and function of alveolar macrophages distinguish them from other macrophage populations and suggest that it is important to classify macrophages according to the site that they occupy.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigens, Surface / physiology
  • Cellular Microenvironment
  • Humans
  • Lectins, C-Type / physiology
  • Macrophage Activation
  • Macrophages, Alveolar / physiology*
  • Mannose Receptor
  • Mannose-Binding Lectins / physiology
  • Membrane Glycoproteins / physiology
  • Orexin Receptors
  • Organ Specificity
  • PPAR gamma / physiology
  • Receptors, Cell Surface / physiology
  • Receptors, Immunologic / physiology
  • Transforming Growth Factor beta / physiology
  • Triggering Receptor Expressed on Myeloid Cells-1


  • Antigens, Surface
  • CD200R1 protein, human
  • Lectins, C-Type
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Membrane Glycoproteins
  • Orexin Receptors
  • PPAR gamma
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • TREM1 protein, human
  • Transforming Growth Factor beta
  • Triggering Receptor Expressed on Myeloid Cells-1