Adenosine triphosphate level and capsaicin-induced changes in mitochondrial membrane potential in mononuclear cells of patients with chronic obstructive pulmonary disease

   Introduction. Cellular energy supply is a key aspect of their functioning, mediated by mitochondria. Despite reports of energy deficiency in COPD, we previously found an increase in mitochondrial membrane potential (ΔΨm) in the leukocytes of affected individuals. At the same time, increased expression of transient receptor potential channels TRPV1 was observed in COPD, raising questions about their potential role in regulating mitochondrial functions.

   Aim. To assess ΔΨm and adenosine triphosphate (ATP) levels in peripheral blood mononuclear cells of COPD patients and to clarify the effect of the TRPV1 agonist capsaicin on ΔΨm.

   Materials and methods. The study included 42 COPD patients of varying severity and 11 control subjects without signs of bronchial obstruction. All participants underwent spirometry and body plethysmography to assess lung function. The amount of ATP was measured by the luminometric method on a plate analyzer, with mean ATP content per cell calculated. ΔΨm was determined by flow cytometry using the ratiometric cationic carbonylcyanine dye JC-1. The dynamics of ΔΨm in response to TRPV1 activation by capsaicin were assessed and the results were expressed as a percentage of ΔΨm in unstimulated cells.

   Results. It was found that the ATP content in the peripheral blood mononuclear cells of COPD patients was higher than in the control group (0.96 (0.36; 1.79) fmol/cell vs. 0.14 (0.11; 0.21) fmol/cell, p = 0.001). Capsaicin caused significant changes in ΔΨm in the mononuclear cells of COPD patients: 33.1 (-19.0; 86.0)% for lymphocytes and 48.2 (0.0; 126.7) % for monocytes (p = 0.001). However, ΔΨm did not differ significantly between COPD patients and the control group either at baseline or under capsaicin stimulation. In COPD patients with higher FEV1 values, ΔΨm was elevated in both lymphocytes (0.69 (0.64; 0.86) vs. 0.51 (0.35; 0.61), p = 0.004) and monocytes (0.28 (0.21; 0.37) vs. 0.18 (0.13; 0.29), p = 0.015).

   Conclusion. We found no evidence of energy deficiency in mononuclear cells from COPD patients, however, in patients with severe and very severe ventilatory impairment, some decrease in ΔΨm may occur without affecting ATP production. Increased ATP production in COPD may be mediated by increased TRPV1 expression and could play a pathological role by activating purinergic signaling.

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