Association of immune cell recruitment and BPD development

Abstract

In the neonatal lung, exposure to both prenatal and early postnatal risk factors converge into the development of injury and ultimately chronic disease, also known as bronchopulmonary dysplasia (BPD). The focus of many studies has been the characteristic inflammatory responses provoked by these exposures. Here, we review the relationship between immaturity and prenatal conditions, as well as postnatal exposure to mechanical ventilation and oxygen toxicity, with the imbalance of pro- and anti-inflammatory regulatory networks. In these conditions, cytokine release, protease activity, and sustained presence of innate immune cells in the lung result in pathologic processes contributing to lung injury. We highlight the recruitment and function of myeloid innate immune cells, in particular, neutrophils and monocyte/macrophages in the BPD lung in human patients and animal models. We also discuss dissimilarities between the infant and adult immune system as a basis for the development of novel therapeutic strategies.

Keywords: Bronchopulmonary dysplasia; Chronic lung disease; Inflammation; Lung; Macrophage; Monocyte; Neonate; Neutrophil.

Fig. 1

Schematic represents the innate immune signals related to lung inflammation culminating in the BPD development and progression. Preterm infants suffer from BPD due to the impact of various risk factors including genetic background, prenatal and postnatal infections, nutrition, oxygen toxicity, and mechanical ventilation. Exposure of the structurally and functionally immature lung to these risk factors provokes oxidative stress and results in the increased expression of pro-inflammatory cytokines by resident cells in the alveolar niche. Subsequently, innate immune cells are recruited including neutrophils as the first-line defense. These events are followed by the extravasation of monocytes which eventually differentiate into macrophages in the tissue context. Neutrophil and monocyte signaling is associated with pulmonary tissue damage including impairment of epithelial and vascular function and progression of inflammatory processes. Black arrows indicate the elevating events during BPD