Lipids and Lipoproteins
Surfactant Protein A Is a Principal and Oxidation-sensitive MicrobialPermeabilizing Factor in the Alveolar LiningFluid*

https://doi.org/10.1074/jbc.M411344200Get rights and content
Under a Creative Commons license
open access

We have reported that surfactant protein A kills some Gram-negativeorganisms by increasing membrane permeability. In this study, we investigatedthe physiologic importance of this activity and the effect of oxidative stresson the antimicrobial functions of SP-A in vitro and in vivo.Concentrated bronchoalveolar lavage fluids from SP-A+/+ mice increased thepermeability of the Escherichia coli K12 cell membrane to a greaterextent than lavage from SP-A-/- animals. Similarly, calcium-dependentsurfactant-binding proteins of SP-A+/+ mice increased membrane permeabilitymore than those from SP-A-/- mice and produced greater zonal killing ofagar-embedded bacteria in a radial diffusion assay. Exposure of human SP-A tocopper-initiated surfactant phospholipid peroxidation or to free radicalsgenerated by human neutrophils in vitro increased the level ofSP-A-associated carbonyl moieties and blocked the permeabilizing function ofthe protein. We also found that exposure of mice to 90% O2 for 4days, sufficient to lead to consumption of glutathione, oxidation of proteinthiols, and accumulation of airspace protein-associated carbonyl moieties,blocked the permeabilizing activity of lavage fluid from SP-A+/+ mice. Weconclude that SP-A is a major microbial permeablizing factor in lavage fluidand that oxidative stress inhibits the antibacterial activity of SP-A by amechanism that includes oxidative modification and functional inactivation ofthe protein.

Cited by (0)

*

This work was supported by a Merit Grant from the Department of VeteransAffairs and National Institutes of Health Grant HL-68861 (to F. X. M.). Thecosts of publication of this article were defrayed in part by the payment ofpage charges. This article must therefore be hereby marked“advertisement” in accordance with 18 U.S.C. Section 1734solely to indicate this fact.