Ancient origin of mast cells

Area of Science:

• Immunology
• Evolutionary Biology
• Cell Biology

Background:

• Mammalian mast cells (MCs) play vital roles in host defense against infections.
• Their evolutionary origins remain largely unexplored.
• Understanding MC origins can illuminate fundamental aspects of innate immunity.

Purpose of the Study:

• To investigate the evolutionary origins of mammalian mast cells.
• To identify potential ancestral counterparts of mast cells in invertebrate species.
• To explore the conservation of mast cell functions throughout evolution.

Main Methods:

• Comparative morphology and histochemistry of sea squirt (Ciona intestinalis) test cells and human mast cells.
• Analysis of mediator content (histamine, heparin, proteases) and exocytosis.
• Molecular biology techniques to identify and characterize relevant cDNAs (histidine decarboxylase, prostaglandin D2 synthase).

Main Results:

• Ciona intestinalis test cells exhibit morphological and histochemical similarities to human cutaneous mast cells.
• Test cells store and release histamine and heparin·serine proteases upon stimulation.
• Activated test cells produce prostaglandin D2 and express genes for key biosynthetic enzymes, mirroring mammalian MCs.
• Molecular data supports the identification of C. intestinalis test cells as functional counterparts of mammalian MCs.

Conclusions:

• Mammalian mast cells likely originated before the emergence of chordates, over 500 million years ago.
• The remarkable conservation of mast cells highlights their ancient and fundamental importance in innate immunity.
• This study provides evidence for a deep evolutionary history of mast cells, predating adaptive immunity.