RT Journal Article
T1 Multivalent, calcium-independent binding of surfactant protein A and D to sulfated glycosaminoglycans of the alveolar epithelial glycocalyx
A1 Avcibas, Rabia
A1 Vermul, Anna
A1 Gluhovic, Vladimir
A1 Boback, Nico
A1 Arroyo, Raquel
A1 Kingma, Paul
A1 Isasi Campillo, Miriam
A1 García Ortega, Lucía
A1 Griese, Matthias
A1 Kuebler, Wolfgang M.
A1 Ochs, Matthias
A1 Lauster, Daniel
A1 Lopez Rodriguez, Elena
AB Lung surfactant collectins, surfactant protein A (SP-A) and D (SP-D), are oligomeric C-type lectins involved in lung immunity. Through their carbohydrate recognition domain, they recognize carbohydrates at pathogen surfaces and initiate lung innate immune response. Here, we propose that they may also be able to bind to other carbohydrates present in typical cell surfaces, such as the alveolar epithelial glycocalyx. To test this hypothesis, we analyzed and quantified the binding affinity of SP-A and SP-D to different sugars and glycosaminoglycans (GAGs) by microscale thermophoresis (MST). In addition, by changing the calcium concentration, we aimed to characterize any consequences on the binding behavior. Our results show that both oligomeric proteins bind with high affinity (in nanomolar range) to GAGs, such as hyaluronan (HA), heparan sulfate (HS) and chondroitin sulfate (CS). Binding to HS and CS was calcium-independent, as it was not affected by changing calcium concentration in the buffer. Quantification of GAGs in bronchoalveolar lavage (BAL) fluid from animals deficient in either SP-A or SP-D showed changes in GAG composition, and electron micrographs showed differences in alveolar glycocalyx ultrastructure in vivo. Taken together, SP-A and SP-D bind to model sulfated glycosaminoglycans of the alveolar epithelial glycocalyx in a multivalent and calcium-independent way. These findings provide a potential mechanism for SP-A and SP-D as an integral part of the alveolar epithelial glycocalyx binding and interconnecting free GAGs, proteoglycans, and other glycans in glycoproteins, which may influence glycocalyx composition and structure.  NEW & NOTEWORTHY SP-A and SP-D function has been related to innate immunity of the lung based on their binding to sugar residues at pathogen surfaces. However, their function in the healthy alveolus was considered as limited to interaction with surfactant lipids. Here, we demonstrated that these proteins bind to glycosaminoglycans present at typical cell surfaces like the alveolar epithelial glycocalyx. We propose a model where these proteins play an important role in interconnecting alveolar epithelial glycocalyx components.
PB American Physiological Society
SN 1040-0605
YR 2024
FD 2024-05-01
LK https://hdl.handle.net/20.500.14352/119607
UL https://hdl.handle.net/20.500.14352/119607
LA eng
NO Avcibas, R., Vermul, A., Gluhovic, V., Boback, N., Arroyo, R., Kingma, P., Isasi-Campillo, M., Garcia-Ortega, L., Griese, M., Kuebler, W. M., Ochs, M., Lauster, D., & Lopez-Rodriguez, E. (2024). Multivalent, calcium-independent binding of surfactant protein A and D to sulfated glycosaminoglycans of the alveolar epithelial glycocalyx. American journal of physiology. Lung cellular and molecular physiology, 326(5), L524-L538. https://doi.org/10.1152/AJPLUNG.00283.2023
NO This work has been funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) within the SFB 1449 – 431232613; sub-projects B01 (to M.O. and W.M.K.) and C04 (to D.L.).
NO Deutsche Forschungsgemeinschaft
DS Docta Complutense
RD 30 mar 2026