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Updated: Sep 25, 2026

Morphological and Compositional Analysis of Neutrophil Extracellular Traps Induced by Microbial and Chemical Stimuli
Published on: November 4, 2022
Role and regulation of TRP channels in neutrophil granulocytes
Inka Heiner1, Jörg Eisfeld, Andreas Lückhoff
1Institut für Physiologie, Universitätsklinikum der RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
Abstract:
Members of the transient receptor potential (TRP) family for which mRNA can be demonstrated in neutrophil granulocytes with RT-PCR include TRPC6 (as only "short" TRP), TRPM2, TRPV1, TRPV2, TRPV5 and TRPV6. When these are analyzed in heterologous overexpression experiments, TRPM2 is the only cation channel with characteristic properties that can be used as fingerprint to provide functional evidence for its expression in neutrophil granulocytes. As cells transfected with TRPM2, neutrophil granulocytes display non-selective cation currents and typical channel activity evoked by intracellular ADP-ribose and NAD. Thus, stimulation of TRPM2 is likely to occur after activation of CD38 (producing ADP-ribose) and during the oxidative burst (enhancing the NAD concentration). This novel mode of cation entry regulation may be of particular importance for the response of granulocytes to chemoattractants. TRPV6 is a likely but not exclusive candidate as subunit of the channels mediating store-operated Ca2+ entry (SOCE). Evidence for SOCE in granulocytes has been presented with the fura-2 technique but not with electrophysiological methods although Ca2+-selective store-operated currents can be demonstrated in HL-60 cells, a cell culture model of neutrophil granulocytes.
Insights
Transient Receptor Potential Melastatin 2 (TRPM2) channels are functionally expressed in neutrophils, responding to cellular signals like ADP-ribose and NAD. This discovery offers new insights into neutrophil granulocyte responses to chemoattractants.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Neutrophil granulocytes play a critical role in the immune response.
- Transient Receptor Potential (TRP) channels are involved in various cellular functions, including ion transport.
- Previous studies indicated the presence of TRP channel mRNA in neutrophils, but functional evidence was limited.
Purpose of the Study:
- To functionally characterize Transient Receptor Potential (TRP) channels expressed in neutrophil granulocytes.
- To investigate the role of specific TRP channels, particularly TRPM2 and TRPV6, in neutrophil function.
- To explore novel mechanisms of cation entry regulation in neutrophils.
Main Methods:
- Reverse transcription polymerase chain reaction (RT-PCR) to detect TRP channel mRNA.
- Heterologous overexpression experiments in cell lines.
- Electrophysiological recordings to analyze cation currents and channel activity.
- Fura-2 technique for calcium imaging.
Main Results:
- mRNA for TRPC6, TRPM2, TRPV1, TRPV2, TRPV5, and TRPV6 was detected in neutrophil granulocytes.
- TRPM2 was identified as the only cation channel with characteristic properties functionally expressed in neutrophils.
- Neutrophil granulocytes transfected with TRPM2 exhibited non-selective cation currents activated by intracellular ADP-ribose and NAD.
- TRPV6 is a potential candidate for mediating store-operated calcium entry (SOCE).
Conclusions:
- TRPM2 channels are functionally expressed in neutrophil granulocytes and are activated by ADP-ribose and NAD, suggesting a role in cellular signaling during oxidative bursts and CD38 activation.
- This novel TRPM2-mediated cation entry pathway may significantly influence neutrophil responses to chemoattractants.
- TRPV6 is a likely, though not exclusive, subunit involved in store-operated calcium entry (SOCE) in granulocytes.
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