Distinct phenotypic expression levels of macrophages in neonatal lungs

Fang,Shih-Yuan; Chen,Jen-Lung; Chiu,Meng-Hsuan; Huang,Chien-Chi; Lin,Ming-Wei; Lam,Chen-Fuh

doi:10.3892/etm.2021.9800

Distinct phenotypic expression levels of macrophages in neonatal lungs

Authors:
- Shih-Yuan Fang
- Jen-Lung Chen
- Meng-Hsuan Chiu
- Chien-Chi Huang
- Ming-Wei Lin
- Chen-Fuh Lam
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Affiliations: Department of Anesthesiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan, R.O.C., Department of Surgery, E‑Da Hospital/E‑Da Cancer Hospital, I‑Shou University, Kaohsiung 824, Taiwan, R.O.C., Department of Medical Research, E‑Da Hospital/E‑Da Cancer Hospital, I‑Shou University, Kaohsiung 824, Taiwan, R.O.C.
Published online on: February 19, 2021 https://doi.org/10.3892/etm.2021.9800
Article Number: 369
Copyright: © Fang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Alveolar macrophages are the front‑line defense against environmental pathogens. However, to the best of our knowledge, differences in function and phenotypic expression levels of macrophages between neonatal and adult lungs have not previously been determined. The present study investigated lung tissues and analyzed blood samples to find cell markers of M1 and M2 macrophages in neonatal and adult rats. Pulmonary sepsis was induced by intrapleural instillation of lipopolysaccharide (LPS; 20 mg/kg) and survival time after administration of LPS was measured. In certain neonates, a selective inducible nitric oxide synthase (iNOS) inhibitor, 1400w, was administered prior to induction of pulmonary sepsis. Compared with adults, fetal and neonatal lung tissues had significantly higher levels of iNOS and CD86 (M1 markers), whereas the expression levels of CD206 and arginase‑1 (M2 markers) were lower in the neonatal lung. The circulating cells that co‑expressed CD68 (monocytes and macrophages) and CD86 in the blood were also significantly higher in neonates than in adults (25.9±6.6 vs. 11.6±2.2%; P=0.007. At basal unstimulated conditions, lung tissue concentrations of nitrite and nitrate (NOx) were significantly lower in the neonates than in adults (112.1±55.9 vs. 340.9±124.9 µM/g; P<0.001). However, NOx was increased following administration of LPS. Administration of 1400w suppressed lung tissue levels of NOx and improved the survival time in neonatal rats treated with LPS. The present study demonstrated that M1 is the primary macrophage phenotype in the neonatal lung and that higher iNOS expression levels do not have a protective effect against pulmonary endotoxins in neonates. Overproduction of NO by iNOS in neonatal alveolar macrophages may result in detrimental effects during pulmonary inflammation.

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