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

Front Immunol. 2012 Jul 16;3:205. doi: 10.3389/fimmu.2012.00205. eCollection 2012.

Abstract

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.

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