The Sand Fly Salivary Protein Lufaxin Inhibits the Early Steps of the Alternative Pathway of Complement by Direct Binding to the Proconvertase C3b-B
| Autor: | Antonio F. Mendes-Sousa, Vladimir Fazito do Vale, Naylene C. S. Silva, Anderson B. Guimaraes-Costa, Marcos H. Pereira, Mauricio R. V. Sant’Anna, Fabiano Oliveira, Shaden Kamhawi, José M. C. Ribeiro, John F. Andersen, Jesus G. Valenzuela, Ricardo N. Araujo |
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| Rok vydání: | 2017 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
0301 basic medicine Immunology alternative pathway chemical and pharmacologic phenomena Biology Lufaxin Complement factor B Divalent 03 medical and health sciences complement system inhibition Immunology and Allergy Original Research chemistry.chemical_classification saliva C3-convertase Complement system 030104 developmental biology chemistry Biochemistry Alternative complement pathway biology.protein Biophysics Properdin Factor D sand fly lcsh:RC581-607 Complement membrane attack complex |
| Zdroj: | Frontiers in Immunology, Vol 8 (2017) Frontiers in Immunology |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2017.01065 |
| Popis: | Saliva of the blood feeding sand fly Lutzomyia longipalpis was previously shown to inhibit the alternative pathway (AP) of the complement system. Here, we have identified Lufaxin, a protein component in saliva, as the inhibitor of the AP. Lufaxin inhibited the deposition of C3b, Bb, Properdin, C5b, and C9b on agarose-coated plates in a dose-dependent manner. It also inhibited the activation of factor B in normal serum, but had no effect on the components of the membrane attack complex. Surface plasmon resonance (SPR) experiments demonstrated that Lufaxin stabilizes the C3b-B proconvertase complex when passed over a C3b surface in combination with factor B. Lufaxin was also shown to inhibit the activation of factor B by factor D in a reconstituted C3b-B, but did not inhibit the activation of C3 by reconstituted C3b-Bb. Proconvertase stabilization does not require the presence of divalent cations, but addition of Ni2+ increases the stability of complexes formed on SPR surfaces. Stabilization of the C3b-B complex to prevent C3 convertase formation (C3b-Bb formation) is a novel mechanism that differs from previously described strategies used by other organisms to inhibit the AP of the host complement system. |
| Databáze: | OpenAIRE |
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