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Updated: Aug 30, 2026
Analyzing the Functions of Mast Cells In Vivo Using 'Mast Cell Knock-in' Mice
Published on: May 27, 2015
Ultrastructural evidence of brain mast cell activation without degranulation in monkey experimental allergic
R Letourneau1, J J Rozniecki, V Dimitriadou
1Department of Pharmacology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
Abstract:
Experimental allergic encephalomyelitis (EAE) is an animal model for the human demyelinating disease multiple sclerosis (MS). Increased permeability of the blood-brain barrier (BBB) precedes the development of clinical or pathologic findings in MS and may be induced by perivascular brain mast cells secreting vasoactive and proinflammatory molecules. Brain mast cells were investigated ultrastructurally in acute EAE of the non-human primate common marmoset Callithrix jacchus, which develops a mild neurologic relapsing-remitting course. Control diencephalic samples contained perivascular mast cells with mostly intact electron dense granules. In contrast, EAE samples had marked demyelination and mast cells with numerous altered secretory granules; their electron dense content varied in amount and texture with a "honeycomb" or "target" appearance, but without degranulation. These changes were evident even before the development of any clinical symptoms and suggest that brain mast cells may be involved in EAE, and possibly MS, through a unique process that may involve selective secretion of molecules able to disrupt the BBB.
Insights
Altered brain mast cells in marmosets with experimental allergic encephalomyelitis (EAE) suggest a role in multiple sclerosis (MS) pathogenesis. These changes occur before symptoms, potentially involving selective molecule release that increases blood-brain barrier permeability.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Experimental allergic encephalomyelitis (EAE) serves as a model for human multiple sclerosis (MS).
- Increased blood-brain barrier (BBB) permeability is an early event in MS pathogenesis.
- Perivascular brain mast cells are implicated in BBB disruption via vasoactive and proinflammatory molecule secretion.
Purpose of the Study:
- To investigate ultrastructural changes in brain mast cells during acute EAE in common marmosets.
- To explore the potential role of mast cell secretory activity in BBB disruption in EAE and MS.
Main Methods:
- Ultrastructural analysis of diencephalic perivascular mast cells.
- Comparison of mast cells from control marmosets and those with acute EAE.
- Assessment of mast cell secretory granules and their morphology.
Main Results:
- Mast cells in EAE marmosets exhibited numerous altered secretory granules with variable electron-dense content and unique "honeycomb" or "target" appearances.
- These ultrastructural changes were observed prior to the onset of clinical symptoms.
- No overt degranulation of mast cells was detected, suggesting a unique secretory process.
Conclusions:
- Brain mast cells undergo significant ultrastructural alterations in EAE, preceding clinical manifestation.
- These mast cell changes suggest a potential role in MS pathogenesis through a non-degranulative secretory mechanism.
- Selective secretion of molecules by mast cells may contribute to blood-brain barrier disruption in EAE and MS.
