Complement activated granulocytes can cause autologous tissue destruction in man

Area of Science:

• Immunology
• Pathophysiology
• Cell Biology

Background:

• Polymorphonuclear granulocytes (PMNs) activation by C5a is implicated in multiple organ failure.
• Understanding the role of C5a in sepsis and trauma pathogenesis is crucial.

Purpose of the Study:

• To investigate the effects of C5a-activated PMNs on human endothelial and mesothelial cells.
• To explore the role of C5a in the early stages of organ damage.

Main Methods:

• Human PMNs were exposed to zymosan-activated plasma (ZAP).
• Chemiluminescence and respiratory burst activity were measured.
• Electron microscopy was used to observe morphological changes in human omentum.

Main Results:

• ZAP induced PMN activation and a respiratory burst, which was abolished by decomplementation and anti-C5a antibodies.
• Electron microscopy revealed PMN aggregation, capillary thrombosis, and diapedesis.
• PMNs caused rapid disruption and destruction of mesothelial cell connections.

Conclusions:

• C5a-activated PMNs can induce significant endothelial and mesothelial damage in humans.
• C5a appears to be an important mediator in the pathogenesis of severe sepsis and trauma.
• Further research is needed to establish a direct causal link between C5a and organ failure.