Elevated Concentrations of Liver-Expressed Chemokine/CC Chemokine Ligand 16 in Bronchoalveolar Lavage Fluid from Patients with Eosinophilic Pneumonia

Abstract

Background: Eosinophilic pneumonia is characterized by the prominent accumulation of eosinophils and lymphocytes in the lung parenchyma. Liver-expressed chemokine (LEC)/CC chemokine ligand 16 (CCL16) is a novel functional ligand for H4 which is expressed on eosinophils and also an affinity ligand for CCR1, CCR2, CCR5 and CCR8 which are expressed on T lymphocytes and monocytes. The purpose of this study is to clarify the role of LEC/CCL16 in eosinophilic pneumonia. Methods: The LEC/CCL16 level was measuredusing an enzyme-linked immunosorbent assay in the bronchoalveolar lavage fluid (BALF) of 33 patients with eosinophilic pneumonia, 26 patients with sarcoidosis and 10 healthy volunteers. The cell sources of LEC/CCL16 in BALF were evaluated by immunocytochemistry. Results: The LEC/CCL16 levels in BALF from patients with eosinophilic pneumonia were significantly higher than those from patients with sarcoidosis and healthy volunteers. The BALF LEC/CCL16 levels correlated with the numbers of BALF eosinophils and lymphocytes, respectively. The BALF LEC/CCL16 levels were significantly decreased after remission in eosinophilic pneumonia. In immunocytochemistry, the LEC/CCL16 expression was clearly observed in CD1a-positive dendritic cells as well as in CD68-positive macrophages harvested from patients with eosinophilic pneumonia, but not from the controls. Conclusions: These results suggest that LEC/CCL16 produced by dendritic cells as well as by alveolar macrophages contributes to the accumulation of eosinophils and lymphocytes into the inflamed lungs of patients with eosinophilic pneumonia.

Elevated concentrations of CCR7 ligands in patients with eosinophilic pneumonia

“…We previously demonstrated that CCL17 and CCL22 produced by DC and AM accumulate in CCR4‐expressing Th2 cells, leading to eosinophilic inflammation . CCL16 produced by DC and AM accumulates in H4‐expressing eosinophils in the lung parenchyma . In this study, although both BALF CCL19 and CCL21 levels were elevated, only CCL19 levels correlated with the CCL16, CCL17 and CCL22 levels in the BALF from patients with EP.…”

“…Eosinophilic pneumonia (EP) is characterized by a prominent accumulation of eosinophils in the lung parenchyma . Several molecules, including cytokines and chemokines, are involved in establishing inflammation in EP . The mechanism underlying eosinophil accumulation in the lungs, however, is not fully understood.…”

“…Th2‐specific chemokines, CCL17 and CCL22, are highly expressed in lung specimens, contributing to eosinophilic inflammation through the induction of interleukin (IL)‐4, IL‐5 and IL‐13 , which may provide clues to the immunopathogenesis of EP. CCL16 has important roles in the accumulation of H4‐expressing eosinophils and CCR1‐, 2‐, 3‐, 4‐ and 5‐expressing lymphocytes in EP . We previously demonstrated that dendritic cells (DC) and alveolar macrophages (AM) are the sources of CCL16 and CCL17 in EP .…”

“…CCL16 has important roles in the accumulation of H4‐expressing eosinophils and CCR1‐, 2‐, 3‐, 4‐ and 5‐expressing lymphocytes in EP . We previously demonstrated that dendritic cells (DC) and alveolar macrophages (AM) are the sources of CCL16 and CCL17 in EP . Dendritic cells and AM are key cells involved in the pathogenesis of inflammation in EP.…”

Plasma CCL16 Chemokine Secretion and Expression in Liver Tissue of Patients with Autoimmune Hepatitis: A Pilot Study

“…These data suggest that this chemokine induces the accumulation of eosinophils and lymphocytes in the lung tissue of patients affected by this pathology. 10 In IBS, CCL16 has been found to be elevated 7.46fold compared to controls, and 130-fold in IBS patients with constipation vs IBS cases with diarrhea. 11 In a study conducted in patients with active UC, biopsy macrophages were found to have significant expression of CCL16 compared to inactive patients; therefore, researchers injected tumor cells into mice that produced CCL16, which induced alterations compatible with UC in these animals.…”