Granzyme B: a new crossroad of complement and apoptosis

Area of Science:

• Immunology
• Molecular Biology
• Trauma Research

Background:

• Severe tissue trauma triggers "molecular danger" sensing pathways, notably the complement and apoptosis cascades.
• The molecular interactions bridging these systems remain poorly understood.
• Existing knowledge lacks clarity on how these pathways interconnect during trauma response.

Purpose of the Study:

• To investigate a novel interaction between the complement system and apoptosis.
• To identify the role of granzyme B in generating complement anaphylatoxins C3a and C5a.
• To explore the clinical relevance of this interaction in trauma patients.

Main Methods:

• In vitro experiments involving human complement components (C3, C5) and granzyme B.
• Concentration-dependent production assays for C3a and C5a.
• Chemotaxis assays using human neutrophils.
• Intracellular granzyme B level determination in leukocytes from trauma patients and healthy volunteers.

Main Results:

• The serine protease granzyme B directly generated C3a and C5a from C3 and C5 in vitro.
• Generated C5a exhibited chemotactic activity for neutrophils.
• Trauma patients showed significantly elevated intracellular granzyme B levels in neutrophils and lymphocytes shortly after injury compared to controls.
• This indicates early co-activation of complement and apoptosis systems post-trauma.

Conclusions:

• A novel interaction interface between the complement and apoptosis systems, mediated by granzyme B, has been identified.
• Granzyme B can generate C3a and C5a independently of classical complement proteases.
• This finding provides a new molecular link between apoptosis and complement activation in the context of severe tissue trauma.