Distinct phenotypic expression levels of macrophages in neonatal lungs
Shih-Yuan Fang1, Jen-Lung Chen2, Meng-Hsuan Chiu1
1Department of Anesthesiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan, R.O.C.
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.
Insights
Neonatal rat lungs primarily feature M1 macrophages, unlike adults. High inducible nitric oxide synthase (iNOS) levels in neonates do not protect against endotoxins, potentially causing harm during lung inflammation.
Area of Science:
- Immunology
- Neonatal Physiology
- Pulmonary Medicine
Background:
- Alveolar macrophages are crucial for lung defense against pathogens.
- Functional and phenotypic differences in neonatal versus adult lung macrophages are not well understood.
- Understanding these differences is vital for neonatal respiratory health.
Purpose of the Study:
- To investigate and compare macrophage phenotypes (M1/M2) in neonatal and adult rat lungs.
- To determine the role of inducible nitric oxide synthase (iNOS) in neonatal pulmonary inflammation.
- To assess the impact of M1 macrophage dominance on endotoxin response in neonates.
Main Methods:
- Analysis of lung tissues and blood samples for M1 (iNOS, CD86) and M2 (CD206, arginase-1) macrophage markers in neonatal and adult rats.
- Induction of pulmonary sepsis using lipopolysaccharide (LPS) to measure survival.
- Administration of an iNOS inhibitor (1400w) in neonates before LPS challenge.
Main Results:
- Neonatal lungs showed higher M1 markers (iNOS, CD86) and lower M2 markers (CD206, arginase-1) compared to adults.
- Neonates had significantly higher circulating CD68+/CD86+ cells and lower basal lung nitrite/nitrate (NOx) levels.
- LPS increased NOx; iNOS inhibition (1400w) reduced NOx and improved survival in LPS-treated neonates.
Conclusions:
- The neonatal lung is characterized by a predominant M1 macrophage phenotype.
- Elevated iNOS expression in neonatal lungs does not confer protection against pulmonary endotoxins.
- Overproduction of nitric oxide (NO) by iNOS in neonatal alveolar macrophages may be detrimental during pulmonary inflammation.
