Endopeptidase inhibition and intestinal antigen processing in mice

Area of Science:

• Gastroenterology
• Immunology
• Protease Function

Background:

• Digestive enzymes play a crucial role in breaking down ingested proteins.
• The systemic availability of protein antigens is influenced by gastrointestinal processing.
• Understanding antigen absorption is key to managing food allergies and autoimmune diseases.

Purpose of the Study:

• To investigate how gastrointestinal digestive processes affect the systemic availability of ingested protein antigens.
• To determine the impact of inhibiting luminal proteolysis on the absorption of ovalbumin.
• To examine the role of pancreatic proteases in modulating antigen absorption.

Main Methods:

• Administered aprotinin, a trypsin inhibitor, intragastrically to mice.
• Measured the uptake of ovalbumin and 14C-polyethylene glycol (MW 4000) from the gastrointestinal tract.
• Assessed serum levels of immunoreactive ovalbumin and intestinal permeability.

Main Results:

• Aprotinin significantly reduced trypsin and chymotrypsin activity in the intestinal lumen.
• Aprotinin administration led to a 12-fold increase in serum ovalbumin levels within 1 hour.
• Increased ovalbumin uptake was not attributed to changes in intestinal permeability, as polyethylene glycol uptake showed minimal increase.

Conclusions:

• Inhibition of luminal proteolysis significantly increases the serum concentration of immunoreactive ovalbumin.
• Acute inhibition of luminal proteases allows larger quantities of intact protein to interact with mucosal absorptive surfaces.
• Pancreatic proteases modulate antigen absorption from the gastrointestinal tract in adult animals.