Macrophage Origin and Development

Creative Biolabs is dedicated to providing the best products and services to clients worldwide in the academic and industries, assisting in the pursuit of breakthrough scientific discoveries about macrophages. Here, we provide an overview of the current knowledge on macrophage origin and development.

Macrophage Origin

Macrophages are derived from different sources during embryonic and postnatal development.

• The earliest macrophages emerge from the yolk sac, a transient structure that forms during the first weeks of gestation and provides nutrients and blood cells to the developing embryo. These yolk sac-derived macrophages (YSMs) are generated from erythro-myeloid progenitors (EMPs) that express the transcription factor GATA1 and produce both erythroid and myeloid cells.
  • YSMs colonize various tissues, such as the brain, liver, lung, and skin, before the establishment of definitive hematopoiesis in the fetal liver and bone marrow.
  • YSMs persist throughout life and can self-renew independently of blood monocytes.
• Another source of macrophages during embryonic development is the fetal liver, which becomes the main site of hematopoiesis from the second trimester of gestation until birth. Fetal liver-derived macrophages (FLMs) are generated from hematopoietic stem cells (HSCs) that express the transcription factor RUNX1 and give rise to all blood cell lineages.
  • FLMs migrate to various tissues, such as the spleen, thymus, and lymph nodes, where they differentiate into tissue-resident macrophages.
  • FLMs can also replenish some of the YSM populations, such as microglia in the brain and Kupffer cells in the liver.

Table 1. Comparison of characteristics and functions of YSMs and FLMs

• Bone marrow is the main source of macrophages after birth, where it produces monocytes and macrophages under the influence of some growth factors.
  • Bone marrow-derived macrophages can be divided into two subtypes, based on whether they express Ly6C: classical or inflammatory monocytes (Ly6C high) and non-classical or patrolling monocytes (Ly6C low).
  • Bone marrow-derived macrophages can maintain and renew tissue-resident macrophage populations under steady-state and inflammatory conditions.
  • Bone marrow-derived macrophages can also adopt different macrophage phenotypes and functions depending on the local signals they encounter in different tissues.

Fig.1 Macrophage lineages, ontogeny, and contribution to populations of resident tissue macrophages.¹

Macrophage Development

Macrophages develop from monocytes, which are the largest type of white blood cell produced in the bone marrow.

• Monocytes circulate in the blood for one to three days before entering the peripheral tissues, where they differentiate into macrophages.
• Macrophages are found in essentially all tissues, where they have different names and functions. For example, microglia in the brain, Kupffer cells in the liver, alveolar macrophages in the lungs, and histiocytes in connective tissues.
• Macrophages play a critical role in both innate and adaptive immunity, as well as tissue development, remodeling, and homeostasis.
• The development of macrophages are regulated by various factors, such as cytokines, growth factors, transcription factors, and environmental cues.

Fig.2 Development of tissue-resident macrophages.²

Monocyte Migration

Monocytes are circulating leukocytes that can migrate from the blood into the tissues in response to various signals, such as inflammation, infection, or tissue damage. Monocyte migration is a multistep process that involves the following stages: egress from the bone marrow, circulation in the blood, adhesion to the endothelium, transendothelial migration, and infiltration into the tissues.

Fig.3 Human monocyte subsets in health.³

• Monocyte egress from the bone marrow is regulated by several factors, such as CCR2, CX3CR1, and S1P.
• Monocyte circulation in the blood is influenced by several factors, such as shear stress, oxygen tension, and cytokines.
• Monocyte adhesion to the endothelium is mediated by a series of interactions between adhesion molecules expressed by both cell types.
• Monocyte transendothelial migration is the process of crossing the endothelial barrier to enter the subendothelial space. Monocyte transendothelial migration can occur through two main pathways: paracellular and transcellular.
• Monocyte infiltration into the tissues is the final step of monocyte migration, which involves the interaction of monocytes with the extracellular matrix and other cell types in the tissue microenvironment.

In conclusion, macrophages are essential immune cells that originate from hematopoietic stem cells and develop into different subsets depending on their tissue environment and stimuli. Macrophages play diverse roles in homeostasis, inflammation, wound healing, and host defense. Understanding the origin and development of macrophages can provide insights into the mechanisms of various diseases and potential therapeutic targets.

Creative Biolabs provides a variety of macrophage markers and other cellular markers to help researchers identify and analyze macrophage function and phenotype.

References

1. Epelman, Slava, et al. "Origin and Functions of Tissue Macrophages." Immunity, (2014).
2. Varol, Chen, et al. "Macrophages: development and tissue specialization." Annu Rev Immunol, (2015).
3. Qiu, Pengfei, et al. "Review: the Role and Mechanisms of Macrophage Autophagy in Sepsis." Inflammation, (2019).