| First Author | Kuzmenko AI | Year | 2005 |
| Journal | J Biol Chem | Volume | 280 |
| Issue | 27 | Pages | 25913-9 |
| PubMed ID | 15890661 | Mgi Jnum | J:109974 |
| Mgi Id | MGI:3630192 | Doi | 10.1074/jbc.M411344200 |
| Citation | Kuzmenko AI, et al. (2005) Surfactant protein A is a principal and oxidation-sensitive microbial permeabilizing factor in the alveolar lining fluid. J Biol Chem 280(27):25913-9 |
| abstractText | We have reported that surfactant protein A kills some Gram-negative organisms by increasing membrane permeability. In this study, we investigated the physiologic importance of this activity and the effect of oxidative stress on the antimicrobial functions of SP-A in vitro and in vivo. Concentrated bronchoalveolar lavage fluids from SP-A+/+ mice increased the permeability of the Escherichia coli K12 cell membrane to a greater extent than lavage from SP-A-/- animals. Similarly, calcium-dependent surfactant-binding proteins of SP-A+/+ mice increased membrane permeability more than those from SP-A-/- mice and produced greater zonal killing of agar-embedded bacteria in a radial diffusion assay. Exposure of human SP-A to copper-initiated surfactant phospholipid peroxidation or to free radicals generated by human neutrophils in vitro increased the level of SP-A-associated carbonyl moieties and blocked the permeabilizing function of the protein. We also found that exposure of mice to 90% O2 for 4 days, sufficient to lead to consumption of glutathione, oxidation of protein thiols, and accumulation of airspace protein-associated carbonyl moieties, blocked the permeabilizing activity of lavage fluid from SP-A+/+ mice. We conclude that SP-A is a major microbial permeablizing factor in lavage fluid and that oxidative stress inhibits the antibacterial activity of SP-A by a mechanism that includes oxidative modification and functional inactivation of the protein. |
