%0 Journal Article %T Elevation of pulmonary CD163 + and CD204 + macrophages is associated with the clinical course of idiopathic pulmonary fibrosis patients %A Nouno, Takashi %A Okamoto, Masaki %A Ohnishi, Koji %A Kaieda, Shinjiro %A Tominaga, Masaki %A Zaizen, Yoshiaki %A Ichiki, Masao %A Momosaki, Seiya %A Nakamura, Masayuki %A Fujimoto, Kiminori %A Fukuoka, Junya %A Shimizu, Shigeki %A Komohara, Yoshihiro %A Hoshino, Tomoaki %J Journal of Thoracic Disease %D 2019 %B 2019 %9 %! Elevation of pulmonary CD163 + and CD204 + macrophages is associated with the clinical course of idiopathic pulmonary fibrosis patients %K %X Background: M2-like/repair macrophages are thought to contribute to fibrotic process of idiopathic pulmonary fibrosis (IPF). We analyzed the association between pulmonary accumulation of M2-like macrophages and survival in IPF patients. Methods: Lung tissues were obtained by surgical lung biopsy from patients with IPF (n=16), nonspecific interstitial pneumonia (NSIP, n=8) and control subjects (n=14). Samples were also obtained at autopsy from 9 patients who died of acute exacerbation (AE) of IPF. Lung specimens and/or human peripheral blood mononuclear cells-derived macrophages were evaluated by immunohistochemistry for expression of CD68 (pan-macrophage marker), CD163, and CD204 (M2-like macrophage markers), and by in situ mRNA hybridization and ELISA for production of transforming growth factor-β1 (TGF-β1). Results: CD68 + , CD163 + , and CD204 + cell counts and CD163 + /CD68 + and CD204 + /CD68 + cell ratios were comparable in IPF and NSIP lung tissues and significantly higher than in control tissues. IPF-AE lung samples contained significantly elevated CD68 + and CD163 + cell counts and CD163 + /CD68 + cell ratio compared with IPF samples, whereas CD204 + cell counts and CD204 + /CD68 + cells ratio did not differ. High CD163 + /CD68 + and CD204 + /CD68 + cell ratios were significantly associated with shorter overall survival and time-to-AE in IPF patients. In vitro -differentiated human CD163 + and CD204 + macrophages both secreted TGF-β1; however, the novel IPF drug pentraxin 2/serum amyloid protein could suppress secretion only by CD204 + macrophages. Conclusions: Pulmonary accumulation of CD163 + and CD204 + macrophages is associated with worse clinical course in IPF patients. Suppression of macrophage activation and TGF-β1 secretion may be a potential therapeutic target for IPF. %U https://jtd.amegroups.org/article/view/31969 %V 11 %N 9 %P 4005-4017 %@ 2077-6624