دورية أكاديمية
Soluble MAC is primarily released from MAC-resistant bacteria that potently convert complement component C5
| العنوان: | Soluble MAC is primarily released from MAC-resistant bacteria that potently convert complement component C5 |
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| المؤلفون: | Dennis J Doorduijn, Marie V Lukassen, Marije FL van 't Wout, Vojtech Franc, Maartje Ruyken, Bart W Bardoel, Albert JR Heck, Suzan HM Rooijakkers |
| المصدر: | eLife, Vol 11 (2022) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | complement, membrane attack complex, terminal complement complex, Escherichia coli, Staphylococcus, C5, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | The membrane attack complex (MAC or C5b-9) is an important effector of the immune system to kill invading microbes. MAC formation is initiated when complement enzymes on the bacterial surface convert complement component C5 into C5b. Although the MAC is a membrane-inserted complex, soluble forms of MAC (sMAC), or terminal complement complex (TCC), are often detected in sera of patients suffering from infections. Consequently, sMAC has been proposed as a biomarker, but it remains unclear when and how it is formed during infections. Here, we studied mechanisms of MAC formation on different Gram-negative and Gram-positive bacteria and found that sMAC is primarily formed in human serum by bacteria resistant to MAC-dependent killing. Surprisingly, C5 was converted into C5b more potently by MAC-resistant compared to MAC-sensitive Escherichia coli strains. In addition, we found that MAC precursors are released from the surface of MAC-resistant bacteria during MAC assembly. Although release of MAC precursors from bacteria induced lysis of bystander human erythrocytes, serum regulators vitronectin (Vn) and clusterin (Clu) can prevent this. Combining size exclusion chromatography with mass spectrometry profiling, we show that sMAC released from bacteria in serum is a heterogeneous mixture of complexes composed of C5b-8, up to three copies of C9 and multiple copies of Vn and Clu. Altogether, our data provide molecular insight into how sMAC is generated during bacterial infections. This fundamental knowledge could form the basis for exploring the use of sMAC as biomarker. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X 49599542 |
| Relation: | https://elifesciences.org/articles/77503; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.77503 |
| URL الوصول: | https://doaj.org/article/e61d4a19506a49599542172c87788013 |
| رقم الأكسشن: | edsdoj.61d4a19506a49599542172c87788013 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X 49599542 |
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| DOI: | 10.7554/eLife.77503 |