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Interstitial lung disease
Lymphangiogenic factors are associated with the severity of hypersensitivity pneumonitis
  1. Masahiro Yamashita1,
  2. Takashi Mouri1,2,
  3. Miyuki Niisato1,
  4. Hiroo Nitanai1,
  5. Hitoshi Kobayashi1,
  6. Masahito Ogasawara3,
  7. Ryujin Endo4,
  8. Kazuki Konishi5,
  9. Tamotsu Sugai6,
  10. Takashi Sawai6 and
  11. Kohei Yamauchi1
  1. 1Department of Pulmonary Medicine, Allergy and Rheumatology, Iwate Medical University School of Medicine, Morioka, Japan
  2. 2Department of Respiratory Medicine, Iwate Prefectural Chubu Hospital, Kitakami, Japan
  3. 3Department of Pharmacology, Ehime University Graduate School of Medicine, Toon, Japan
  4. 4Department of Gastroenterology and Hepatology, Iwate Medical University School of Medicine, Morioka, Japan
  5. 5Department of Pulmonary Medicine, Morioka Tsunagi Onsen Hospital, Morioka, Japan
  6. 6Department of Pathology, Iwate Medical University School of Medicine, Morioka, Japan
  1. Correspondence to Dr Masahiro Yamashita; yamam{at}iwate-med.ac.jp

Abstract

Background Antigen presenting cells play a pivotal role in the adaptive immune response in hypersensitivity pneumonitis (HP). It was hypothesised that lymphangiogenesis is involved in the pathophysiology of HP via cell transport.

Objective To determine the clinical significance of lymphangiogenic factors in HP.

Methods Levels of vascular endothelial growth factors (VEGF)-A, VEGF-C, VEGF-D and CCL21 in the serum and bronchoalveolar lavage fluid (BALF) were measured in 29 healthy volunteers, 14 patients with idiopathic pulmonary fibrosis (IPF) and 26 patients with HP by ELISA. Additionally, immunohistochemical analyses were performed using lung specimens of patients with HP (n=8) and IPF (n=10).

Results BALF VEGF-D levels were significantly elevated in patients with HP compared to the other groups. BALF VEGF–D levels in patients with HP correlated significantly with the BALF total cell and lymphocyte counts (r=0.485, p=0.014 and r=0.717, p<0.0001, respectively). BALF VEGF-C and CCL21 levels were increased in patients with HP compared to healthy volunteers, but not patients with IPF. BALF CCL21 levels were negatively correlated with the forced expiratory volume in 1 s percentage and diffuse capacity of the lung for carbon monoxide (r=−0.662, p=0.007 and r=−0.671, p=0.024, respectively). According to the immunohistochemical analyses, CCL21 was expressed in the lymphatic endothelium in both conditions and CCR7+ cells were aggregated around lymphatics in patients with HP, but not in patients with IPF.

Conclusions Lymphangiogenic factors might be associated with the inflammatory and functional severity of HP. The increased BALF VEGF-D levels were associated with lymphatic alveolitis intensity, and CCL21 with lung function impairment.

  • Allergic Alveolitis

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/bmjresp-2015-000085

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