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Expression of transient receptor potential C6 channels in human lung macrophages
Tricia K Finney-Hayward1, Mariana Oana Popa, Parmjit Bahra
1National Heart and Lung Institute, Imperial College London, UK.
Abstract:
Chronic obstructive pulmonary disease (COPD) is associated with pulmonary inflammation with increased numbers of macrophages located in the parenchyma. These macrophages have the capacity to mediate the underlying pathophysiology of COPD; therefore, a better understanding of their function in chronic inflammation associated with this disease is vital. Ion channels regulate many cellular functions; however, their role in macrophages is unclear. This study examined the expression and function of transient receptor potential (TRP) channels in human macrophages. Human alveolar macrophages and lung tissue macrophages expressed increased mRNA and protein for TRPC6 when compared with monocytes and monocyte-derived macrophages. Moreover, TRPC6 mRNA expression was significantly elevated in alveolar macrophages from patients with COPD compared with control subjects. There were no differences in mRNA for TRPC3 or TRPC7. Although mRNA for TRPM2 and TRPV1 was detected in these cells, protein expression could not be determined. Fractionation of lung-derived macrophages demonstrated that TRPC6 protein was more highly expressed by smaller macrophages compared with larger macrophages. Using whole-cell patch clamp electrophysiology, TRPC6-like currents were measured in both macrophage subpopulations with appropriate biophysical and basic pharmacological profiles. These currents were active under basal conditions in the small macrophages. These data suggest that TRPC6-like channels are functional on human lung macrophages, and may be associated with COPD.
Insights
Transient Receptor Potential C6 (TRPC6) channels are more abundant in lung macrophages of chronic obstructive pulmonary disease (COPD) patients. These TRPC6 channels are functional and may play a role in COPD-related inflammation.
Area of Science:
- Immunology
- Cell Biology
- Respiratory Medicine
Background:
- Chronic obstructive pulmonary disease (COPD) involves lung inflammation with increased macrophages.
- Understanding macrophage function in COPD is crucial for disease management.
- The role of ion channels, specifically transient receptor potential (TRP) channels, in macrophage function is not well understood.
Purpose of the Study:
- To investigate the expression and function of TRP channels in human macrophages.
- To determine if TRP channel expression differs in macrophages from COPD patients.
- To explore the potential role of TRP channels in COPD pathophysiology.
Main Methods:
- Examined mRNA and protein expression of TRP channels (TRPC6, TRPC3, TRPC7, TRPM2, TRPV1) in human monocytes and macrophages.
- Compared TRP channel expression in alveolar macrophages from COPD patients and control subjects.
- Utilized whole-cell patch clamp electrophysiology to assess TRPC6 channel function.
Main Results:
- Human alveolar and lung tissue macrophages showed increased TRPC6 mRNA and protein compared to monocytes.
- TRPC6 mRNA was significantly higher in alveolar macrophages from COPD patients versus controls.
- Functional TRPC6-like currents were detected in lung macrophages, particularly smaller ones, under basal conditions.
Conclusions:
- TRPC6 channels are expressed and functional in human lung macrophages.
- TRPC6 expression is elevated in macrophages from COPD patients.
- TRPC6 channels represent a potential therapeutic target for COPD.
