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Increased expression of A Proliferation-inducing Ligand (APRIL) in lung leukocytes and alveolar epithelial cells in COPD patients with non small cell lung cancer: a possible link between COPD and lung cancer?

Polverino F (1), Laucho-Contreras M (2), Rojas Quintero J (2), Divo M (3), Pinto-Plata V (3), Sholl L (4), de-Torres JP (5), Celli BR (3), Owen CA (3).
(1) Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Room 855B, Harvard Institutes of Medicine Building, 77 Avenue Louis Pasteur, Boston, MA 02115 USA ; Lovelace Respiratory Research Institute, Albuquerque, NM USA ; University of Parma, Parma, Italy.
(2) Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Room 855B, Harvard Institutes of Medicine Building, 77 Avenue Louis Pasteur, Boston, MA 02115 USA.
(3) Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Room 855B, Harvard Institutes of Medicine Building, 77 Avenue Louis Pasteur, Boston, MA 02115 USA ; Lovelace Respiratory Research Institute, Albuquerque, NM USA.
(4) Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA USA.
(5)Clinica Universidad de Navarra, Pamplona, Spain. 

Revista: Multidisciplinary Respiratory Medicine

Fecha: 04/04/2016

Neumología

BACKGROUND:
Chronic Obstructive Pulmonary Disease (COPD) is characterized by an excessive activation of the adaptive immune system and, in particular, uncontrolled expansion of the B-cell pool.

One of the key promoters of B cell expansion is A PRoliferation-Inducing Ligand (APRIL). APRIL has been strongly linked to non small cell lung cancer (NSCLC) onset and progression previously. However, little is known about the expression of APRIL in the lungs of COPD patients.


METHODS:
Using immuno-fluorescence staining, the expression of APRIL was assessed in sections of lungs from 4 subjects with primary diagnosis of COPD (FEV1 33 ± 20 % predicted), 4 subjects with primary diagnosis of NSCLC, 4 subjects diagnosed with both COPD and NSCLC, smokers without COPD or NSCLC and 3 healthy never-smokers.

The percentage of B cells, alveolar macrophages (AMs) and polymorphonuclear neutrophils (PMNs) in the lung and alveolar epithelial cells (AECs) that stained positively for APRIL was quantified using epi-fluorescence microscopy and image analysis software.

RESULTS:
The percentage of APRIL-expressing B cells, AMs, PMNs and alveolar epithelial cells (AECs) was higher in patients having both COPD and NSCLC than in patients with either COPD or NSCLC alone, SC or NSC (p < 0.03 for all comparisons).

The percentage of APRIL-expressing AMs and AECs (but not in B cells) was higher in patients with NSCLC alone than in patients with COPD alone. The percentage of APRIL-expressing AECs (but not B cells or AMs) was higher in COPD patients than in SC and NSC (p < 0.05 for all comparisons). The percentage of APRIL-expressing B cells, AMs and AECs cells was similar in NSC and SC.

CONCLUSION:
The percentage of APRIL-expressing B cells, AMs and AECs is higher in the lungs of patients with both COPD and NSCLC than in patients with COPD or NSCLC alone or control subjects. These findings suggest that APRIL may contribute to the pathogenesis of both COPD and NSCLC, and possibly to the development of NSCLC in patients with established COPD.

CITA DEL ARTÍCULO  Multidiscip Respir Med. 2016 Apr 4;11:17. doi: 10.1186/s40248-016-0051-6. eCollection 2016

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