Intracellular Ca(2+) operates a switch between repair and lysis of streptolysin O-perforated cells

Area of Science:

• Cell biology
• Immunology
• Biochemistry

Background:

• Pathogenic pore-forming peptides can damage host cell plasma membranes.
• The cellular outcomes, such as proliferation or cell death, are determined by unknown factors.
• Intracellular calcium concentration ([Ca2+]i) plays a critical role in cellular responses.

Purpose of the Study:

• To investigate the factors determining cell fate following plasma membrane damage by pore-forming peptides.
• To elucidate the role of intracellular calcium concentration ([Ca2+]i) in cellular responses to membrane damage.
• To identify the mechanisms underlying cell survival or death.

Main Methods:

• Monitoring intracellular calcium concentration ([Ca2+]i) in real-time.
• Observing plasma membrane repair mechanisms and microparticle shedding.
• Analyzing ceramide platform formation and internalization.

Main Results:

• Cells with [Ca2+]i below a critical threshold (10 microM) successfully repair membrane damage and recover.
• Plasma membrane repair involves sealing calcium entry 'hot spots' and shedding microparticles.
• Elevated [Ca2+]i above the threshold leads to irreversible ceramide platform formation and cell death.
• Incomplete repair with sustained elevated [Ca2+]i results in oscillations and continuous microparticle shedding.

Conclusions:

• The extent of intracellular calcium ([Ca2+]i) elevation is the key determinant of cell fate after pore-forming peptide attack.
• Ca2+-dependent mechanisms dictate whether cells survive or undergo programmed cell death.
• Plasma membrane repair and calcium regulation are crucial for cell survival.