Up-regulated membrane and nuclear leukotriene B4 receptors in COPD.
OBJECTIVE
We investigated the role of two leukotriene B4 (LTB4) receptors, BLT1 and peroxisome proliferator-activated receptor (PPAR)-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 PPARalpha.


METHODS
BLT1 and PPARalpha 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 PPARalpha-positive alveolar macrophages and PPARalpha-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 PPARalpha 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.


CONCLUSIONS
The results demonstrated that BLT1 and PPARalpha 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.
Marian
Emanuela
E
Dipartimento di Medicina Ambientale e Sanità Pubblica, Università degli Studi di Padova, via Giustiniani, 2, 35128 Padova, Italy. piero.maestrelli@unipd.it
Baraldo
Simonetta
S
Visentin
Annalisa
A
Papi
Alberto
A
Saetta
Marina
M
Fabbri
Leonardo M
LM
Maestrelli
Piero
P
D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology; D047493:PPAR alpha / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000378:metabolism* / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D018102:Receptors, Leukotriene B4 / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D012129:Respiratory Function Tests; D012907:Smoking / Q000378:metabolism*
C513240:LTB4R protein, human; D047493:PPAR alpha; D018102:Receptors, Leukotriene B4; D018048:Receptors, Purinergic P2