J Korean Med Sci.  2023 Aug;38(31):e242. 10.3346/jkms.2023.38.e242.

Properties of Pleural Mesothelial Cells in Idiopathic Pulmonary Fibrosis and Cryptogenic Organizing Pneumonia

• Loloci G
• Kim YM
• Choi WI
• Jang HJ
• Park SJ
• Kwon KY

• KMID: 2544961
• DOI: http://doi.org/10.3346/jkms.2023.38.e242

Abstract

Background
Profibrotic properties of pleural mesothelial cells may play an important role in the fibrosis activity in idiopathic pulmonary fibrosis (IPF). The purpose of this study was to compare the expression of pleural mesothelial cell markers in IPF and cryptogenic organizing pneumonia (COP), with an assumption that increased expression implies increase in fibrosis.
Methods
Twenty IPF lung samples were stained by immunohistochemistry for the pleural mesothelial cell markers: leucine rich repeat neuronal 4 (LRRN4), uroplakin 3B, CCchemokine ligand 18, and laminin-5. Nine COP lung samples were used as controls. A semiquantitative analysis was performed to compare markers expression in IPF and COP.
Results
LRRN4 expression was found in epithelial lining cells along the honeycombing and fibroblastic foci in IPF, but not in the fibrotic interstitial lesion and airspace filling fibrous tufts in COP. We found a significant decrease in baseline forced vital capacity when LRRN4 expression was increased in honeycombing epithelial cells and fibroblastic foci.
Conclusion
LRRN4 expression patterns in IPF are distinct from those in COP. Our findings suggest that mesothelial cell profibrotic property may be an important player in IPF pathogenesis and may be a clue in the irreversibility of fibrosis in IPF.

Keyword

Pleural Mesothelial Cell; LRRN4; Uroplakin 3B; CCL18; Idiopathic Pulmonary Fibrosis

Figure

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  Fig. 1 Comparison of microscopic findings of representative IPF and COP. (A, B) IPF: Patchy fibrosis and preserved alveolar structures are seen in the lung parenchyma (A). In enlarged view, irregular fibrotic thickening was observed, and fibroblastic foci (arrows) could be observed (B). (C, D) COP: Fibrous tufts (arrows) filling the alveolar cavity can be observed diffusely.IPF = idiopathic pulmonary fibrosis, COP = cryptogenic organizing pneumonia.

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  Fig. 2 Comparison of immunohistochemical staining results for LRRN 4, UPK3B, CCL18, and laminin-5 in between IPF and COP samples. LRRN4: In IPF, positive expression in the epithelial cells along the honeycombing (A) and cells covering the fibroblastic foci (B, arrow). In COP, no expression in the epithelial cells surrounding fibrous tufts (C). UPK3B: In IPF, mild expression in the epithelial cells covering honeycombings (D) and positive expression in the pleural mesothelial cells (E, arrows). In COP, weak expression in the fibrous tufts (F). CCL18: In IPF, positive expression in the smooth muscle bundles (G, arrows), positive expression in the alveolar epithelial cells (arrow), and alveolar macrophages (arrow heads) in fibrotic lesion (H). In COP, no expression in the fibrotic area (I). Laminin-5: In IPF, focal expression in honeycombing (J, arrows) and in the epithelial cells covering fibroblastic foci (K, arrows). In COP, diffuse expression in the epithelial cells surrounding the fibrous tufts (L). LRRN4 and UPK3B were clearly stained in the visceral pleura both IPF and COP samples. All markers were no or scanty staining in normal epithelium. Original magnification: A-C and F-L (×100); D and E (×40).LRRN4 = leucine rich repeat neuronal 4, UPK3B = uroplakin 3B, CCL18 = CC-chemokine ligand 18, IPF = idiopathic pulmonary fibrosis, COP = cryptogenic organizing pneumonia.

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  Fig. 3 Staining score group and FVC % predicted. (A) The staining score of LRRN4 in the epithelial cells along the honeycombing and FVC % predicted. Twenty patients with idiopathic pulmonary fibrosis were divided into 3 groups based on LRRN4 staining score in the epithelium. Staining scores 1, 2, and 3 represent 3, 6, and 11 patients, respectively. (B) The staining score of LRRN4 in fibrotic foci and FVC % predicted. Twenty patients with idiopathic pulmonary fibrosis were divided into 3 groups based on LRRN4 staining score in the fibrotic foci. Staining scores 1, 2, and 3 represent 4, 6, and 10 patients, respectively.FVC = forced vital capacity, LRRN4 = leucine rich repeat neuronal 4.There was a significant difference between LRRN4 staining group 1 and group 2: aP = 0.016 vs. group 3, bP = 0.035 vs. group 3. There was a significant difference between LRRN4 staining group 1 vs. group 3 cP = 0.026.

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