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Expression of adhesion molecules on human fetal cerebral vessels: relationship to microglial colonisation during
P Rezaie1, N J Cairns, D K Male
1Department of Neuropathology, Institute of Psychiatry, London, UK. spkadkm@iop.bpmf.ac.uk
Abstract:
Microglia represent the primary immune effector cells of the adult central nervous system (CNS). The origin of these cells has been a subject of intense debate over the last century. However, immunohistochemical and chimera developmental studies in rodents support the hypothesis that microglia are monocytic in origin. There have been relatively few studies to date on microglia in human fetal development, and the mechanisms by which microglial precursors enter the developing CNS are as yet unknown. It is possible that microglial precursors use combinations of adhesion molecules on cerebral endothelium to gain entry into the developing CNS. In the present study, we have shown the distribution of microglia within human fetal cerebral cortex between 16 and 22 weeks of gestation using RCA-1 lectin histochemistry. We have also demonstrated dual anti-macrophage antibody labelling of these cells in conjunction with adhesion molecules ICAM-1, ICAM-2 and PECAM on cerebral endothelium throughout this period. We conclude that fetal microglia usually occur at highly vascularised sites within the developing human fetal brain and are more specifically associated with the expression of ICAM-2 on cerebral endothelium.
Insights
Fetal microglia, the brain's immune cells, originate from monocytic precursors. These precursors likely enter the developing human brain via specific adhesion molecules on blood vessels, particularly ICAM-2.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Microglia are the primary immune cells of the central nervous system (CNS).
- Rodent studies suggest microglia originate from monocytic precursors.
- Limited research exists on human fetal microglia and their CNS entry mechanisms.
Purpose of the Study:
- To investigate the distribution of microglia in the developing human fetal brain.
- To identify the adhesion molecules involved in microglial precursor entry into the CNS.
Main Methods:
- RCA-1 lectin histochemistry to identify microglia in human fetal cerebral cortex (16-22 weeks gestation).
- Dual labeling with anti-macrophage antibodies and adhesion molecules (ICAM-1, ICAM-2, PECAM) on cerebral endothelium.
Main Results:
- Microglia were found in highly vascularized areas of the fetal brain.
- Microglial presence correlated with the expression of ICAM-2 on cerebral endothelium.
Conclusions:
- Fetal microglia are associated with vascularized regions in the developing human brain.
- ICAM-2 on cerebral endothelium appears crucial for microglial precursor migration into the CNS.