Expression of transient receptor potential C6 channels in human lung macrophages.
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.
National Heart and Lung Institute, Imperial College London, UK.
Tricia K
TK
Finney-Hayward
Mariana Oana
MO
Popa
Parmjit
P
Bahra
Su
S
Li
Christopher T
CT
Poll
Martin
M
Gosling
Andrew G
AG
Nicholson
Richard E K
RE
Russell
Onn Min
OM
Kon
Gabor
G
Jarai
John
J
Westwick
Peter J
PJ
Barnes
Louise E
LE
Donnelly
D000328:Adult; D015153:Blotting, Western; D016022:Case-Control Studies; D004594:Electrophysiology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016676:Macrophages, Alveolar / Q000166:cytology / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050052:TRPC Cation Channels / Q000235:genetics* / Q000378:metabolism*; D000074287:TRPC6 Cation Channel; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; C498501:TRPC7 protein, human; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human