Structural Analysis and Lipid-Binding Properties of Recombinant Human Surfactant Protein A Derived from One or Both Genes†

Biochemistry ◽  
2002 ◽  
Vol 41 (47) ◽  
pp. 14041-14053 ◽  
Author(s):  
I. García-Verdugo ◽  
G. Wang ◽  
J. Floros ◽  
C. Casals
Keyword(s):  
Structural Analysis ◽  
Protein A ◽  
Surfactant Protein ◽  
Lipid Binding ◽  
Surfactant Protein A ◽  
Binding Properties

scholarly journals Effect of Acidic pH on the Structure and Lipid Binding Properties of Porcine Surfactant Protein A

1998 ◽  
Vol 273 (24) ◽  
pp. 15183-15191 ◽  
Author(s):  
Miguel L. F. Ruano ◽  
Jesus Pérez-Gil ◽  
Cristina Casals
Keyword(s):  
Protein A ◽  
Surfactant Protein ◽  
Lipid Binding ◽  
Surfactant Protein A ◽  
Acidic Ph ◽  
Binding Properties

scholarly journals Interaction of SP-A (surfactant protein A) with bacterial rough lipopolysaccharide (Re-LPS), and effects of SP-A on the binding of Re-LPS to CD14 and LPS-binding protein

2005 ◽  
Vol 391 (1) ◽  
pp. 115-124 ◽  
Author(s):  
Ignacio García-Verdugo ◽  
Fernando Sánchez-Barbero ◽  
Katrin Soldau ◽  
Peter S. Tobias ◽  
Cristina Casals
Keyword(s):  
Binding Protein ◽  
Protein A ◽  
Fluorescence Analysis ◽  
Surfactant Protein ◽  
Lipid Binding ◽  
Coli Strain ◽  
Surfactant Protein A ◽  
Human Macrophage ◽  
Independent Manner ◽  
Lps Binding

SP-A (surfactant protein A) is a lipid-binding collectin primarily involved in innate lung immunity. SP-A interacts with the bacterial rough LPS (lipopolysaccharide) Re-LPS (Re595 mutant of LPS from Salmonella minnesota), but not with smooth LPS. In the present study, we first examined the characteristics of the interaction of human SP-A with Re-LPS. Fluorescence intensity and anisotropy measurements of FITC-labelled Re-LPS in the presence and absence of SP-A indicated that SP-A bound to Re-LPS in solution in a Ca2+-independent manner, with a dissociation constant of 2.8×10−8 M. In the presence of calcium, a high-mobility complex of SP-A and [3H]Rb-LPS (Rb mutant of LPS from Escherichia coli strain LCD 25) micelles was formed, as detected by sucrose density gradients. Re-LPS aggregation induced by SP-A was further characterized by light scattering. On the other hand, human SP-A inhibited TNF-α (tumour necrosis factor-α) secretion by human macrophage-like U937 cells stimulated with either Re-LPS or smooth LPS. We further examined the effects of human SP-A on the binding of Re-LPS to LBP (LPS-binding protein) and CD14. SP-A decreased the binding of Re-LPS to CD14, but not to LBP, as detected by cross-linking experiments with 125I-ASD-Re-LPS [125I-labelled sulphosuccinimidyl-2-(p-azidosalicylamido)-1,3-dithiopropionate derivative of Re-LPS] and fluorescence analysis with FITC-Re-LPS. When SP-A, LBP and CD14 were incubated together, SP-A reduced the ability of LBP to transfer 125I-ASD-Re-LPS to CD14. These SP-A effects were not due to the ability of SP-A to aggregate Re-LPS in the presence of calcium, since they were observed in both the absence and the presence of calcium. These studies suggest that SP-A could contribute to modulate Re-LPS responses by altering the competence of the LBP–CD14 receptor complex.

scholarly journals Elucidation of Lipid Binding Sites on Lung Surfactant Protein A Using X-ray Crystallography, Mutagenesis, and Molecular Dynamics Simulations

Biochemistry ◽  
2016 ◽  
Vol 55 (26) ◽  
pp. 3692-3701 ◽  
Author(s):  
Boon Chong Goh ◽  
Huixing Wu ◽  
Michael J. Rynkiewicz ◽  
Klaus Schulten ◽  
Barbara A. Seaton ◽  
...  
Keyword(s):  
Binding Sites ◽  
Lung Surfactant ◽  
Protein A ◽  
Surfactant Protein ◽  
Lipid Binding ◽  
Surfactant Protein A ◽  
X Ray ◽  
X Ray Crystallography ◽  
Lung Surfactant Protein ◽  
Dynamics Simulations

scholarly journals Surfactant protein A reduces TLR4 and inflammatory cytokine mRNA levels in neonatal mouse ileum

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lidan Liu ◽  
Chaim Z. Aron ◽  
Cullen M. Grable ◽  
Adrian Robles ◽  
Xiangli Liu ◽  
...  
Keyword(s):  
Proinflammatory Cytokine ◽  
Inflammatory Cytokine ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Mrna Levels ◽  
Wild Type ◽  
Cytokine Mrna ◽  
Protein Levels ◽  
Cytokine Levels

AbstractLevels of intestinal toll-like receptor 4 (TLR4) impact inflammation in the neonatal gastrointestinal tract. While surfactant protein A (SP-A) is known to regulate TLR4 in the lung, it also reduces intestinal damage, TLR4 and inflammation in an experimental model of necrotizing enterocolitis (NEC) in neonatal rats. We hypothesized that SP-A-deficient (SP-A−/−) mice have increased ileal TLR4 and inflammatory cytokine levels compared to wild type mice, impacting intestinal physiology. We found that ileal TLR4 and proinflammatory cytokine levels were significantly higher in infant SP-A−/− mice compared to wild type mice. Gavage of neonatal SP-A−/− mice with purified SP-A reduced ileal TLR4 protein levels. SP-A reduced expression of TLR4 and proinflammatory cytokines in normal human intestinal epithelial cells (FHs74int), suggesting a direct effect. However, incubation of gastrointestinal cell lines with proteasome inhibitors did not abrogate the effect of SP-A on TLR4 protein levels, suggesting that proteasomal degradation is not involved. In a mouse model of experimental NEC, SP-A−/− mice were more susceptible to intestinal stress resembling NEC, while gavage with SP-A significantly decreased ileal damage, TLR4 and proinflammatory cytokine mRNA levels. Our data suggests that SP-A has an extrapulmonary role in the intestinal health of neonatal mice by modulating TLR4 and proinflammatory cytokines mRNA expression in intestinal epithelium.

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