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Isolation and In Vitro Culture of Murine and Human Alveolar Macrophages
09:09

Isolation and In Vitro Culture of Murine and Human Alveolar Macrophages

Published on: April 20, 2018

Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life

Martin Guilliams1, Ismé De Kleer, Sandrine Henri

  • 1Laboratory of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, 9050 Ghent, Belgium.

The Journal of Experimental Medicine
|September 18, 2013
PubMed

Insights

Alveolar macrophages (AMFs) primarily develop from fetal monocytes, not adult circulating monocytes. GM-CSF is crucial for AMF development, guiding fetal monocytes to adopt a stable, self-maintaining phenotype post-birth.

Area of Science:

  • Immunology
  • Developmental Biology
  • Pulmonary Medicine

Background:

  • Tissue-resident macrophages, including alveolar macrophages (AMFs), originate from either adult monocytes or primitive yolk sac macrophages.
  • The specific developmental origin and ontogeny of AMFs in the lung remain incompletely understood.

Purpose of the Study:

  • To elucidate the precise ontogeny of alveolar macrophages (AMFs) in mice.
  • To identify the precursor cells responsible for colonizing the alveolar space and differentiating into AMFs.
  • To investigate the role of cytokines like GM-CSF in AMF development.

Main Methods:

  • BrdU labeling and parabiosis experiments in adult mice.
  • Analysis of lung tissue at various embryonic and postnatal stages.
  • Adoptive transfer of precursor cells into neonatal mice.
  • Genetic manipulation (GM-CSF deficiency) and cytokine therapy studies.

Main Results:

  • Circulating adult monocytes contribute minimally to the steady-state AMF pool.
  • Fetal monocytes, not primitive macrophages, are the primary precursors of AMFs, colonizing the lung mid-gestation.
  • AMF differentiation begins around E18.5, with full colonization by postnatal day 3.
  • GM-CSF is essential for early AMF commitment, and perinatal GM-CSF therapy can rescue AMF development, albeit with an immature phenotype.

Conclusions:

  • Alveolar macrophages predominantly originate from fetal monocytes that colonize the lung during development.
  • Fetal monocytes differentiate into AMFs postnatally, guided by instructive cytokines like GM-CSF, and establish a self-maintaining pool.
  • This study reveals a distinct developmental pathway for tissue-resident macrophages originating from fetal precursors.

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