Surfactant Protein D and Bronchopulmonary Dysplasia: A New Way to Approach an Old Problem

Surfactant protein D and bronchopulmonary dysplasia: a new way to approach an old problem

Surfactant protein D (SP-D) is a collectin protein synthesized by alveolar type II cells in the lungs. SP-D participates in the innate immune defense of the lungs by helping to clear infectious pathogens and modulating the immune response. SP-D has shown an anti-inflammatory role by down-regulating the release of pro-inflammatory mediators in different signaling pathways such as the TLR4, decreasing the recruitment of inflammatory cells to the lung, and modulating the oxidative metabolism in the lungs. Recombinant human SP-D (rhSP-D) has been successfully produced mimicking the structure and functions of native SP-D. Several in vitro and in vivo experiments using different animal models have shown that treatment with rhSP-D reduces the lung inflammation originated by different insults, and that rhSP-D could be a potential treatment for bronchopulmonary dysplasia (BPD), a rare disease for which there is no effective therapy up to date. BPD is a complex disease in preterm infants whose incidence increases with decreasing gestational age at birth. Lung inflammation, which is caused by different prenatal and postnatal factors like infections, lung hyperoxia and mechanical ventilation, among others, is the key player in BPD. Exacerbated inflammation causes lung tissue injury that results in a deficient gas exchange in the lungs of preterm infants and frequently leads to long-term chronic lung dysfunction during childhood and adulthood. In addition, low SP-D levels and activity in the first days of life in preterm infants have been correlated with a worse pulmonary outcome in BPD. Thus, SP-D mediated functions in the innate immune response could be critical aspects of the pathogenesis in BPD and SP-D could inhibit lung tissue injury in this preterm population. Therefore, administration of rhSP-D has been proposed as promising therapy that could prevent BPD.

Publication Summary:

• In this review article, the authors examine the current treatment landscape for bronchopulmonary dysplasia (BPD), a disease that manifests in preterm infants and lacks an effective therapy.
• The authors discuss data demonstrating the critical anti-inflammatory role of surfactant protein D (SP-D), a collectin protein, in the immune defense of the lungs.
• Several in vitro and in vivo studies have shown that recombinant human SP-D (rhSP-D) successfully mimics the role of endogenous SP-D and holds therapeutic promise as a preventative treatment for BPD.

 

Raquel Arroyo and Paul S Kingma

Respiratory Research