The role of protease in immunoregulation

Area of Science:

• Immunology
• Biochemistry
• Protease Inhibition

Background:

• Immunodepression is common in trauma and chronic disease patients, but its mechanisms are unclear.
• Plasma from severely ill patients exhibits lymphocyte suppressive activity.
• Alpha 2-macroglobulin (alpha 2 M) and low molecular weight peptides are implicated in this suppressive activity.

Purpose of the Study:

• To investigate the mechanism of plasma-induced immunosuppression in severely ill patients.
• To elucidate the role of alpha 2-macroglobulin (alpha 2 M) in immune suppression.
• To understand how protease handling affects immunosuppression.

Main Methods:

• Analysis of plasma from severely ill patients.
• Quantification of alpha 2-macroglobulin (alpha 2 M) concentrations.
• Study of alpha 2 M's functional role in binding and degrading proteases.
• Investigation of protease inhibitor function in patients with acute and chronic illnesses.

Main Results:

• Most lymphocyte suppressive activity in severe illness is due to alpha 2-macroglobulin (alpha 2 M) and low molecular weight peptides.
• Alpha 2 M concentration decreased in trauma patients during periods of high plasma suppressive activity.
• In normal plasma, minor protease complex formation with alpha 2 M significantly increased suppressive activity and peptide formation.
• Patients with acute or chronic illnesses showed inadequate protease handling, leading to persistent alpha 2 M-protease complexes or inhibitory peptides.

Conclusions:

• Inadequate handling of proteases by alpha 2-macroglobulin (alpha 2 M) leads to immunosuppression in severe illness.
• Alpha 2 M-protease complexes and inhibitory peptides contribute to the lymphocyte suppressive activity observed in patients.
• Altering protease metabolism presents potential avenues for immunoregulation in disease states.