Study objectives: We investigated the role. of two leukotriene B4 (LTB4) receptors, BLT1 and peroxisome proliferator-activated receptor (PPA-R)-alpha, in conferring the susceptibility to develop COPD in smokers. Proinflammatory LTB4 activities are mediated by BLT1, while the inactivation of LTB4 is promoted by PPAR alpha. Patients and methods: BLT1 and PPAR alpha proteins were quantified by immunohistochemistry in specimens obtained during lung surgery from 19 smokers with or without COPD and from 7 nonsmoking subjects. Results: We have shown that the percentages of PPAR alpha-positive alveolar macrophages and PPARa-positive cells in the alveolar wall were increased in COPD patients compared with control subjects. Moreover, the patients with COPD exhibited a significant increase of BLT1-positive alveolar macrophages compared with nonsmokers and an increased number of BLT1-positive cells in the alveolar walls compared with non-COPD smokers. In contrast, BLT1 and PPAR alpha-immunoreactivity did not differ significantly between nonsmokers and non-COPD smokers. Most of BLT1-positive cells in the alveolar,walls were neutrophils and CD8 cells. While the number of neutrophils infiltrating the lung parenchyma was similar among the three groups, the number of CD8 T cells was increased in COPD patients, but there was no evidence that BLT1 was up-regulated specifically on these cells in COPD patients. Conclusion: The results demonstrated that BLT1 and PPAR alpha are detectable in alveolar macrophages and CD8 T cells in human lung tissue, and suggest that the dual LTB4 receptor system is up-regulated in the peripheral lungs of smokers who are susceptible to the development of COPD. This system might represent a novel target for therapeutic intervention in COPD patients.

Up-regulated membrane and nuclear leukotriene B4 receptors in COPD / Marian, E; Baraldo, S; Visentin, A; Papi, A; Saetta, M; Fabbri, Leonardo; Maestrelli, P.. - In: CHEST. - ISSN 0012-3692. - STAMPA. - 129:6(2006), pp. 1523-1530. [10.1378/chest.129.6.1523]

Up-regulated membrane and nuclear leukotriene B4 receptors in COPD

FABBRI, Leonardo;
2006

Abstract

Study objectives: We investigated the role. of two leukotriene B4 (LTB4) receptors, BLT1 and peroxisome proliferator-activated receptor (PPA-R)-alpha, in conferring the susceptibility to develop COPD in smokers. Proinflammatory LTB4 activities are mediated by BLT1, while the inactivation of LTB4 is promoted by PPAR alpha. Patients and methods: BLT1 and PPAR alpha proteins were quantified by immunohistochemistry in specimens obtained during lung surgery from 19 smokers with or without COPD and from 7 nonsmoking subjects. Results: We have shown that the percentages of PPAR alpha-positive alveolar macrophages and PPARa-positive cells in the alveolar wall were increased in COPD patients compared with control subjects. Moreover, the patients with COPD exhibited a significant increase of BLT1-positive alveolar macrophages compared with nonsmokers and an increased number of BLT1-positive cells in the alveolar walls compared with non-COPD smokers. In contrast, BLT1 and PPAR alpha-immunoreactivity did not differ significantly between nonsmokers and non-COPD smokers. Most of BLT1-positive cells in the alveolar,walls were neutrophils and CD8 cells. While the number of neutrophils infiltrating the lung parenchyma was similar among the three groups, the number of CD8 T cells was increased in COPD patients, but there was no evidence that BLT1 was up-regulated specifically on these cells in COPD patients. Conclusion: The results demonstrated that BLT1 and PPAR alpha are detectable in alveolar macrophages and CD8 T cells in human lung tissue, and suggest that the dual LTB4 receptor system is up-regulated in the peripheral lungs of smokers who are susceptible to the development of COPD. This system might represent a novel target for therapeutic intervention in COPD patients.
2006
129
6
1523
1530
Up-regulated membrane and nuclear leukotriene B4 receptors in COPD / Marian, E; Baraldo, S; Visentin, A; Papi, A; Saetta, M; Fabbri, Leonardo; Maestrelli, P.. - In: CHEST. - ISSN 0012-3692. - STAMPA. - 129:6(2006), pp. 1523-1530. [10.1378/chest.129.6.1523]
Marian, E; Baraldo, S; Visentin, A; Papi, A; Saetta, M; Fabbri, Leonardo; Maestrelli, P.
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/2653
Citazioni
  • ???jsp.display-item.citation.pmc??? 15
  • Scopus 34
  • ???jsp.display-item.citation.isi??? 30
social impact