Is intracellular Ca2+ the trigger for oxygen radical production by polymorphonuclear leucocytes?

Area of Science:

• Immunology
• Cell Biology
• Biochemistry

Background:

• Polymorphonuclear leucocytes (PMNs) are crucial immune cells involved in inflammatory responses.
• Intracellular calcium (Ca2+) is a key signaling molecule in cellular processes, including immune cell activation.
• The precise role of intracellular Ca2+ in PMN activation and oxygen radical production requires further clarification.

Purpose of the Study:

• To critically evaluate the existing evidence for the role of intracellular Ca2+ in PMN activation.
• To investigate the specific contribution of intracellular Ca2+ to oxygen radical production by PMNs.
• To differentiate between Ca2+-dependent and Ca2+-independent activation mechanisms in PMNs.

Main Methods:

• Indirect evidence was gathered through extracellular Ca2+ manipulation, 45Ca flux measurements, and the use of pharmacological agents like Ca2+-ionophores and antagonists.
• Chlortetracycline fluorescence was monitored to assess Ca2+ dynamics.
• Direct measurements of intracellular free Ca2+ were performed using Ca2+-activated photoprotein (obelin) and Ca2+-sensitive fluorescent indicators (quin 2).

Main Results:

• Indirect experimental methods did not provide definitive evidence that increased intracellular Ca2+ is the sole trigger for PMN activation.
• Direct measurements revealed two distinct PMN activation mechanisms.
• One mechanism is triggered by a rise in intracellular Ca2+, with Ca2+ originating mainly from extracellular sources or intracellular stores.
• The second mechanism operates independently of a rise in intracellular Ca2+.

Conclusions:

• The role of intracellular Ca2+ in PMN activation is complex, involving at least two distinct pathways.
• While a rise in intracellular Ca2+ can trigger PMN activation, it is not the only mechanism.
• Understanding these distinct Ca2+ signaling pathways is crucial for comprehending PMN function in immunity and inflammation.