4.8 Article

The salivary scavenger and agglutinin binds MBL and regulates the lectin pathway of complement in solution and on surfaces

Journal

FRONTIERS IN IMMUNOLOGY
Volume 3, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2012.00205

Keywords

complement regulation; gp340; lectin pathway; mannan-binding lectin; mucosal immunity; salivary agglutinin; scavenger receptor cysteine-rich

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Funding

  1. Helsinki Biomedical Graduate School
  2. Helsinki University Central Hospital funds (EVO)
  3. HUSLAB funds
  4. Sigrid Juselius Foundation
  5. Magnus Ehrnrooth Foundation
  6. Academy of Finland

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The salivary scavenger and agglutinin (SALSA), also known as gp340, salivary agglutinin and deleted in malignant brain tumor 1, is a 340-kDa glycoprotein expressed on mucosal surfaces and secreted into several body fluids. SALSA binds to a broad variety of microbes and endogenous ligands, such as complement factor C1q, surfactant proteins D and A, and IgA. Our search for novel ligands of SALSA by direct protein-interaction studies led to the identification of mannan-binding lectin (MBL) as a new binding partner. We observed that surface-associated SALSA activates complement via binding of MBL. On the other hand, soluble SALSA was found to inhibit Candida albicans-induced complement activation. Thus, SALSA has a dual complement activation modifying function. It activates the lectin pathway when bound to a surface and inhibits it when free in the fluid phase. These activities are mediated via a direct interaction with MBL. This suggests that SALSA could target the innate immune responses to certain microorganisms and simultaneously limit complement activation in the fluid phase.

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