| 1. |
- Nordenfelt, Pontus, et al.
(författare)
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Antibody orientation at bacterial surfaces is related to invasive infection.
- 2012
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 209:13, s. 2367-2381
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Tidskriftsartikel (refereegranskat)abstract
- Several of the most significant bacterial pathogens in humans, including Streptococcus pyogenes, express surface proteins that bind IgG antibodies via their fragment crystallizable (Fc) region, and the dogma is that this protects the bacteria against phagocytic killing in blood. However, analysis of samples from a patient with invasive S. pyogenes infection revealed dramatic differences in the presence and orientation of IgG antibodies at the surface of bacteria from different sites. In the throat, IgG was mostly bound to the bacterial surface via Fc, whereas in the blood IgG was mostly bound via fragment antigen-binding (Fab). In infected and necrotic tissue, the Fc-binding proteins were removed from the bacterial surface. Further investigation showed that efficient bacterial IgGFc-binding occurs only in IgG-poor environments, such as saliva. As a consequence, the bacteria are protected against phagocytic killing, whereas in blood plasma where the concentration of IgG is high, the antibodies preferentially bind via Fab, facilitating opsonization and bacterial killing. IgG-poor environments represent the natural habitat for IgGFc-binding bacteria, and IgGFc-binding proteins may have evolved to execute their function in such environments. The lack of protection in plasma also helps to explain why cases of severe invasive infections with IgGFc-binding bacteria are so rare compared with superficial and uncomplicated infections.
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| 2. |
- Persson, Kristin, et al.
(författare)
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Severe lung lesions caused by Salmonella are prevented by inhibition of the contact system
- 2000
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 192:10, s. 1415-1424
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Tidskriftsartikel (refereegranskat)abstract
- Vascular damage induced by trauma, inflammation, or infection results in an alteration of the endothelium from a nonactivated to a procoagulant, vasoconstrictive, and proinflammatory state, and can lead to life-threatening complications. Here we report that activation of the contact system by Salmonella leads to massive infiltration of red blood cells and fibrin deposition in the lungs of infected rats. These pulmonary lesions were prevented when the infected animals were treated with H-D-Pro-Phe-Arg-chloromethylketone, an inhibitor of coagulation factor XII and plasma kallikrein, suggesting that inhibition of contact system activation could be used therapeutically in severe infectious disease.
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