Cellulose acetate beads activate the complement system but inactivate the anaphylatoxins generated

Area of Science:

• Immunology
• Biochemistry

Background:

• Extracorporeal circulation therapies, like granulocyte/monocyte apheresis, can activate the complement system, leading to C5a generation.
• Cellulose acetate beads are used in these therapies, but their impact on complement activation and potential side effects are not fully understood.

Purpose of the Study:

• To investigate the mechanism of complement activation by cellulose acetate beads.
• To compare the anaphylatoxin generation and inactivation pathways in plasma treated with cellulose acetate beads versus zymosan.

Main Methods:

• Preparation of plasma from cellulose acetate bead-treated blood (P-CAB) and comparison with zymosan-activated plasma (ZAP).
• Measurement of anaphylaxis activity via skin tests.
• Assay of carboxypeptidase activity (C5a inactivator) using a colorimetric method.
• Quantification of pro-carboxypeptidase R and neutrophil elastase using ELISA.
• Inhibition studies using a neutrophil elastase inhibitor.

Main Results:

• C5a was generated in P-CAB, but its anaphylaxis activity was lower than in ZAP.
• Carboxypeptidase activity and pro-carboxypeptidase R levels were suppressed in P-CAB, unlike in ZAP.
• Neutrophil elastase levels increased in P-CAB.
• A neutrophil elastase inhibitor reversed the decrease in carboxypeptidase activity and anaphylatoxin inactivation.

Conclusions:

• Cellulose acetate beads activate carboxypeptidase R through elastase release.
• This process leads to the inactivation of anaphylatoxins, potentially explaining the lack of reported side effects.
• The findings elucidate a protective mechanism during extracorporeal therapies involving cellulose acetate beads.