Purinergic Receptor Inhibition Prevents the Development of Smoke-Induced Lung Injury and Emphysema

  • Cicko S
  • Lucattelli M
  • Müller T
  • et al.
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Abstract

Extracellular ATP acts as a “danger signal” and can induce inflammation by binding to purinergic receptors. Chronic obstructive pulmonary disease is one of the most common inflammatory diseases associated with cigarette smoke inhalation, but the underlying mechanisms are incompletely understood. In this study, we show that endogenous pulmonary ATP levels are increased in a mouse model of smoke-induced acute lung inflammation and emphysema. ATP neutralization or nonspecific P2R-blockade markedly reduced smoke-induced lung inflammation and emphysema. We detected an upregulation the purinergic receptors subtypes on neutrophils (e.g., P2Y2R), macrophages, and lung tissue from animals with smoke-induced lung inflammation. By using P2Y2R deficient (−/−) animals, we show that ATP induces the recruitment of blood neutrophils to the lungs via P2Y2R. Moreover, P2Y2R deficient animals had a reduced pulmonary inflammation following acute smoke-exposure. A series of experiments with P2Y2R−/− and wild type chimera animals revealed that P2Y2R expression on hematopoietic cell plays the pivotal role in the observed effect. We demonstrate, for the first time, that endogenous ATP contributes to smoke-induced lung inflammation and then development of emphysema via activation of the purinergic receptor subtypes, such as P2Y2R.

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Cicko, S., Lucattelli, M., Müller, T., Lommatzsch, M., De Cunto, G., Cardini, S., … Idzko, M. (2010). Purinergic Receptor Inhibition Prevents the Development of Smoke-Induced Lung Injury and Emphysema. The Journal of Immunology, 185(1), 688–697. https://doi.org/10.4049/jimmunol.0904042

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