RT Journal Article
T1 Pulmonary surfactant inactivation by β-D-glucan and protective role of surfactant protein A
A1 Cañadas Benito, Olga
A1 Sáenz Martínez, Alejandra
A1 Lorenzo Avilés, Alba de
A1 Casals Carro, María Cristina
AB Pulmonary fungal infections lead to damage of the endogenous lung surfactant system. However, the molecular mechanism underlying surfactant inhibition is unknown. β-D-glucan is the major component of pathogenic fungal cell walls and is also present in organic dust, which increases the risk of respiratory diseases. The objective of this study was to characterize the interaction of this D-glucopyranose polymer with pulmonary surfactant. Our results show that β-D-glucan induced a concentration-dependent inhibition of the surface adsorption, respreading, and surface tension-lowering activity of surfactant preparations containing surfactant proteins SP-B and SP-C. Our data support a new mechanism of surfactant inhibition that consists in the extraction of phospholipid molecules from surfactant membranes by β-D-glucan. As a result, surfactant membranes became more fluid, as demonstrated by fluorescence anisotropy, and showed decreased Tm and transition enthalpy. Surfactant preparations containing surfactant protein A (SP-A) were more resistant to β-D-glucan inhibition. SP-A bound to different β-D-glucans with high affinity (Kd = 1.5 ± 0.1 nM), preventing and reverting β-D-glucan inhibitory effects on surfactant interfacial adsorption and partially abrogating β-D-glucan inhibitory effects on surfactant’s reduction of surface tension. We conclude that β-D-glucan inhibits the biophysical function of surfactant preparations lacking SP-A by subtraction of phospholipids from surfactant bilayers and monolayers. The increased resistance of SP-A-containing surfactant preparations to β-D-glucan reinforces its use in surfactant replacement therapy.
PB Elsevier
SN 0927-7765
YR 2022
FD 2022-11-21
LK https://hdl.handle.net/20.500.14352/71285
UL https://hdl.handle.net/20.500.14352/71285
LA eng
NO CRUE-CSIC (Acuerdos Transformativos 2021)
NO Ministerio de Ciencia e Innovación (MICINN)
DS Docta Complutense
RD 13 abr 2025