Monoclonal antibodies demonstrate protection of polymorphonuclear leukocytes against complement attack

Area of Science:

• Immunology
• Cell Biology

Background:

• Complement system's membrane attack complex (MAC) typically causes lysis in erythrocytes.
• Nucleated cells exhibit resistance to complement, but the underlying molecular mechanisms remain unclear.

Purpose of the Study:

• To elucidate the molecular basis of complement resistance in nucleated cells.
• To investigate the protective mechanisms employed by polymorphonuclear leukocytes (PMNs) against complement attack.

Main Methods:

• Utilized a monoclonal antibody against the terminal complement component C9.
• Quantified C9 using 125I and visualized it with fluorescein.
• Observed cellular responses in PMNs upon complement activation.

Main Results:

• Demonstrated complement attack complex removal via vesiculation in PMNs.
• Observed a Ca2+-dependent rise in cytoplasmic calcium within seconds of MAC formation.
• Showed activation of reactive oxygen metabolite production without concomitant cell lysis.

Conclusions:

• PMNs employ vesiculation to remove the MAC, a key mechanism for complement resistance.
• Calcium signaling plays a crucial role in mediating cellular responses without lysis.
• Findings offer insights into the evolutionary and pathological roles of terminal complement components.