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

Abstract

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.

Lung surfactant proteins as potential targets of prallethrin: An in silico approach

“…Besides, SP-D protects from detrimental effects of various allergens [ 36 ]. It down-regulates proinflammatory cytokines and prevents tissue injury [ 37 ]. CRD of SP-D binds with RSV glycoprotein in a calcium-dependent manner and blocks infection [ 38 ].…”

Commentary: Pattern Recognition Proteins: First Line of Defense Against Coronaviruses

“…Because of the evidence for multiple important anti-inflammatory and immune-modulatory effects, rhSP-D is being evaluated for several other potential clinical uses. For example, there is significant evidence suggesting SP-D deficiency in premature neonates requiring mechanical ventilation is a risk factor to develop bronchopulmonary dysplasia (BPD), a complex disease in which lung inflammation plays an important role ( 22 , 25 ). A recent review by Arroyo and Kingma outlined the potential of SP-D as a therapy for BPD and the evidence published of lung protection in appropriate pre-term animal models ( 23 ).…”

“…Experiments in sheep and mice have demonstrated efficacy of a single dose of about 0.25-2 mg/kg following a single insult such as viral infection, LPS administration, or mechanical ventilation. The doses have been selected considering the previous literature and animal studies ( 22 , 23 ).…”

In silico study reveals binding potential of rotenone at multiple sites of pulmonary surfactant proteins: A matter of concern

“…SP-D also escalates allergen removal and modulates allergic inflammation ( Hawgood et al, 2004 ). It down-regulates proinflammatory cytokine release and subsequent lung tissue injury through different signaling pathways such as TLR4 ( Arroyo and Kingma, 2021 ). SP-D inactivity in severe asthma is involved in disease persistence.…”