Orphan designation: Recombinant fragment of human surfactant protein-D, Prevention of bronchopulmonary dysplasia

2019 ◽  
Author(s):  
Keyword(s):  
Bronchopulmonary Dysplasia ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Recombinant Fragment ◽  
Orphan Designation

scholarly journals A Recombinant Fragment of Human Surfactant Protein D Lacking the Short Collagen-Like Stalk Fails to Correct Morphological Alterations in Lungs of SP-D Deficient Mice

2009 ◽  
Vol 292 (2) ◽  
pp. 183-189 ◽  
Author(s):  
Lars Knudsen ◽  
Katharina Wucherpfennig ◽  
Rose-Marie Mackay ◽  
Paul Townsend ◽  
Christian Mühlfeld ◽  
...  
Keyword(s):  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Recombinant Fragment ◽  
Morphological Alterations ◽  
Deficient Mice

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

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Raquel Arroyo ◽  
Paul S. Kingma
Keyword(s):  
Immune Response ◽  
Preterm Infants ◽  
Bronchopulmonary Dysplasia ◽  
Lung Tissue ◽  
Lung Inflammation ◽  
Tissue Injury ◽  
Surfactant Protein ◽  
Immune Defense ◽  
Innate Immune ◽  
Surfactant Protein D

AbstractSurfactant 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.

Protective effects of a recombinant fragment of human surfactant protein D in a murine model of pulmonary hypersensitivity induced by dust mite allergens

2003 ◽  
Vol 86 (3) ◽  
pp. 299-307 ◽  
Author(s):  
Mamta Singh ◽  
Taruna Madan ◽  
Patrick Waters ◽  
Shreemanta K. Parida ◽  
P.Usha Sarma ◽  
...  
Keyword(s):  
Murine Model ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Protective Effects ◽  
Recombinant Fragment ◽  
Dust Mite

Surfactant protein D increases phagocytosis and aggregation of pollen-allergen starch granules

2005 ◽  
Vol 288 (4) ◽  
pp. L692-L698 ◽  
Author(s):  
Veit J. Erpenbeck ◽  
Delphine C. Malherbe ◽  
Stefanie Sommer ◽  
Andreas Schmiedl ◽  
Wolfram Steinhilber ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Allergic Inflammation ◽  
Allergic Airway Inflammation ◽  
Surfactant Protein ◽  
Phleum Pratense ◽  
Surfactant Protein D ◽  
Starch Granules ◽  
Recombinant Fragment ◽  
Surfactant Lipid ◽  
Induced Aggregation

Recent studies have shown that surfactant components, in particular the collectins surfactant protein (SP)-A and -D, modulate the phagocytosis of various pathogens by alveolar macrophages. This interaction might be important not only for the elimination of pathogens but also for the elimination of inhaled allergens and might explain anti-inflammatory effects of SP-A and SP-D in allergic airway inflammation. We investigated the effect of surfactant components on the phagocytosis of allergen-containing pollen starch granules (PSG) by alveolar macrophages. PSG were isolated from Dactylis glomerata or Phleum pratense, two common grass pollen allergens, and incubated with either rat or human alveolar macrophages in the presence of recombinant human SP-A, SP-A purified from patients suffering from alveolar proteinosis, a recombinant fragment of human SP-D, dodecameric recombinant rat SP-D, or the commercially available surfactant preparations Curosurf and Alveofact. Dodecameric rat recombinant SP-D enhanced binding and phagocytosis of the PSG by alveolar macrophages, whereas the recombinant fragment of human SP-D, SP-A, or the surfactant lipid preparations had no effect. In addition, recombinant rat SP-D bound to the surface of the PSG and induced aggregation. Binding, aggregation, and enhancement of phagocytosis by recombinant rat SP-D was completely blocked by EDTA and inhibited by d-maltose and to a lesser extent by d-galactose, indicating the involvement of the carbohydrate recognition domain of SP-D in these functions. The modulation of allergen phagocytosis by SP-D might play an important role in allergen clearance from the lung and thereby modulate the allergic inflammation of asthma.

ErbB4 deletion leads to changes in lung function and structure similar to bronchopulmonary dysplasia

2008 ◽  
Vol 294 (3) ◽  
pp. L516-L522 ◽  
Author(s):  
Erkhembulgan Purevdorj ◽  
Katja Zscheppang ◽  
Heinz G. Hoymann ◽  
Armin Braun ◽  
Dietlinde von Mayersbach ◽  
...  
Keyword(s):  
Animal Model ◽  
Growth Factor ◽  
Lung Function ◽  
Preterm Infants ◽  
Bronchopulmonary Dysplasia ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Cardiac Defects ◽  
Surfactant Synthesis ◽  
Old Adult

Neuregulin is an important growth factor in fetal surfactant synthesis, and downregulation of its receptor, ErbB4, impairs fetal surfactant synthesis. We hypothesized that pulmonary ErbB4 deletion will affect the developing lung leading to an abnormal postnatal lung function. ErbB4-deleted lungs of 11- to 14-wk-old adult HER4heart mice, rescued from their lethal cardiac defects, were studied for the effect on lung function, alveolarization, and the surfactant system. ErbB4 deletion impairs lung function and structure in HER4heart mice resulting in a hyperreactive airway system and alveolar simplification, as seen in preterm infants with bronchopulmonary dysplasia. It also leads to a downregulation of surfactant protein D expression and an underlying chronic inflammation in these lungs. Our findings suggest that this animal model could be used to further study the pathogenesis of bronchopulmonary dysplasia and might help design protective interventions.

scholarly journals A recombinant fragment of Human surfactant protein D binds Spike protein and inhibits infectivity and replication of SARS-CoV-2 in clinical samples

2020 ◽  
Author(s):  
Taruna Madan ◽  
Barnali Biswas ◽  
Praveen M. Varghese ◽  
Rambhadur Subedi ◽  
Hrishikesh Pandit ◽  
...  
Keyword(s):  
Immune Surveillance ◽  
Cell Receptor ◽  
Surfactant Protein ◽  
Spike Protein ◽  
Clinical Samples ◽  
Surfactant Protein D ◽  
Amino Acid Residues ◽  
Recombinant Fragment ◽  
Acute Infectious Disease

AbstractRationaleCOVID-19 is an acute infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Human surfactant protein D (SP-D) is known to interact with spike protein of SARS-CoV, but its immune-surveillance against SARS-CoV-2 is not known.ObjectiveThis study aimed to examine the potential of a recombinant fragment of human SP-D (rfhSP-D) as an inhibitor of replication and infection of SARS-CoV-2.MethodsrfhSP-D interaction with spike protein of SARS-CoV-2 and hACE-2 receptor was predicted via docking analysis. The inhibition of interaction between spike protein and ACE-2 by rfhSP-D was confirmed using direct and indirect ELISA. The effect of rfhSP-D on replication and infectivity of SARS-CoV-2 from clinical samples was studied by measuring the expression of RdRp gene of the virus using qPCR.Measurements and Main ResultsIn-silico interaction studies indicated that three amino acid residues in the RBD of spike of SARS-CoV-2 were commonly involved in interacting with rfhSP-D and ACE-2. Studies using clinical samples of SARS-CoV-2 positive cases (asymptomatic, n=7 and symptomatic, n=8 and negative controls n=15) demonstrated that treatment with 5μM rfhSP-D inhibited viral replication by ~5.5 fold and was more efficient than Remdesivir (100 μM). Approximately, a 2-fold reduction in viral infectivity was also observed after treatment with 5μM rfhSP-D.ConclusionsThese results conclusively demonstrate that the calcium independent rfhSP-D mediated inhibition of binding between the receptor binding domain of the S1 subunit of the SARS-CoV-2 spike protein and human ACE-2, its host cell receptor, and a significant reduction in SARS-CoV-2 infection and replication in-vitro.

Serum surfactant protein D as a marker for bronchopulmonary dysplasia

2017 ◽  
Vol 32 (5) ◽  
pp. 815-819 ◽  
Author(s):  
Suja Vinod ◽  
Andrew Gow ◽  
Barry Weinberger ◽  
Debra Potak ◽  
Mark Hiatt ◽  
...  
Keyword(s):  
Bronchopulmonary Dysplasia ◽  
Surfactant Protein ◽  
Surfactant Protein D
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