Generation of biologically active, complement-(C5) derived peptides by cathepsin H

Area of Science:

• Biochemistry
• Immunology
• Inflammation Research

Background:

• Cathepsin H is a thiol proteinase found in rat liver lysosomes.
• Intracutaneous injection of cathepsin H in newborn rats causes acute inflammation and polymorphonuclear leukocyte (PMN) accumulation.

Purpose of the Study:

• To investigate if cathepsin H generates complement (C)-derived chemotactic factors, contributing to PMN accumulation during inflammation.
• To determine the role of cathepsin H in activating complement component 5 (C5) and its subsequent effects.

Main Methods:

• Incubation of human and rat EDTA-plasma with purified rat liver cathepsin H.
• Treatment of isolated human C5 with cathepsin H.
• Assays for PMN chemotactic activity and lysosomal enzyme release.
• Intracutaneous injections in newborn rats to assess inflammatory responses.

Main Results:

• Cathepsin H generated C5-derived peptides with PMN chemotactic activity in a concentration- and time-dependent manner in EDTA-plasma.
• Active cathepsin H, but not heat-inactivated enzyme or enzyme with a thiol proteinase inhibitor, generated chemotactic activity.
• Cathepsin H also induced PMN lysosomal enzyme release from isolated C5.
• Higher concentrations of cathepsin H degraded the generated chemotactic peptides.
• PMN accumulation was more pronounced with cathepsin H-treated C5 compared to cathepsin H alone.

Conclusions:

• Cathepsin H generates C-derived chemotactic activity by activating C5, contributing to PMN recruitment in inflammatory responses.
• The enzyme's dual role in both generating and degrading chemotactic factors influences the inflammatory process.
• These findings highlight cathepsin H as a mediator of inflammation through complement system activation.