Processing of human protryptase in mast cells involves cathepsins L, B, and C

Area of Science:

• Biochemistry
• Cell Biology
• Immunology

Background:

• Human β-tryptase is stored in mast cell secretory granules.
• β-Protryptase processing to mature tryptase involves cathepsins (CTS), but the specific CTS involved in human mast cells remains unclear.

Purpose of the Study:

• To investigate the roles of CTSB, CTSL, and CTSC in the processing of human β-protryptase within human mast cells.

Main Methods:

• Utilized short hairpin RNA (shRNA) to silence CTSB, CTSL, and CTSC in HMC-1 cells.
• Employed CTS-specific pharmacologic inhibitors in HMC-1 cells and primary skin-derived mast cells.
• Examined protease expression and localization in HMC-1 cells and skin mast cells.

Main Results:

• Silencing CTSB or CTSL, or using CTS-specific inhibitors, significantly reduced mature β-tryptase formation in HMC-1 and skin mast cells.
• Silencing CTSC had minimal impact on protryptase processing, suggesting it is not the primary protease involved.
• CTSL and CTSB were found to be abundant in skin mast cells and colocalized to secretory granules, unlike CTSC.

Conclusions:

• CTSL and CTSB are the primary proteases responsible for processing human β-protryptase in human mast cells.
• CTSL and CTSB represent potential therapeutic targets for modulating mature tryptase production in vivo.