Salivary agglutinin is the major component in human saliva that modulates the lectin pathway of the complement system

Abstract

Saliva interacts with blood after mucosal damage or leakage of gingival crevicular fluid. Surface-adsorbed salivary agglutinin (SAG) activates the lectin pathway (LP) of the complement system via mannose-binding lectin, while SAG in solution inhibits complement activation. In the present study we investigated if, next to SAG, whole and glandular saliva itself and other salivary glycoproteins activate or inhibit the LP. Complement activation was measured by detecting C4 deposition on microtiter plates coated with saliva or purified proteins. Complement inhibition was measured after incubating serum with saliva or proteins in microtiter plates coated with mannan, an LP activator. Adsorbed whole, sublingual and submandibular saliva showed LP-dependent complement activation. Blood group secretors, but not non-secretors, activated the LP. Saliva of both secretors and non-secretors inhibited C4 deposition on mannan. After depletion of SAG, saliva no longer inhibited the LP. Other salivary proteins, including amylase, MUC5B and histatin 2, did not activate or inhibit the LP. Surface-adsorbed whole saliva and glandular saliva samples activate the LP of complement, depending on the presence of SAG and the secretor status of the donor. In solution, saliva inhibits the LP, depending on the presence of SAG, but independent of the secretor status.

SALSA—A dance on a slippery floor with changing partners

“…In contrast, the lectin pathway inhibition of fluid phase SALSA does not seem to depend on secretor status. (Gunput et al, 2016). This presents a mechanism for individual differences in the ability to utilize SALSA for complement regulation.…”

“…However, as observed for microbial agglutination, activation of complement also appears to depend on the specific localization of SALSA. Thus, when SALSA was free in serum, it was shown to inhibit complement activation (Gunput et al, 2016;Reichhardt et al, 2012). The dual effects of SALSA on the complement system may appear contradictory at first glance.…”

Mannose-binding lectin serum levels and (Gly54asp) gene polymorphism in recurrent aphthous stomatitis: A case-control study

“…12 The mannose-binding lectin (MBL) is a component of the innate immune system and a member of the collectin family of complement system proteins. 13,14 It plays a crucial role in first-line host defense by its antimicrobial properties and binds to particular sugar groups on various pathogens, initiating opsonization and phagocytosis. It can also modulate inflammatory responses.…”

Novel Two-Component System of Streptococcus sanguinis Affecting Functions Associated with Viability in Saliva and Biofilm Formation

“…Both speB and sic are required for the persistence of S. pyogenes in whole saliva and are involved in complement evasion (40). Serum is classically considered the major source of complement proteins synthesized in the liver, but these proteins are also produced in other host tissues and are found to be active in saliva and dental tissues (16,41,42) and to be incorporated into dental pellicles (43). The genome of S. sanguinis SK36 does not harbor speB or sic orthologues (44), and there is limited information about mechanisms by which S. sanguinis copes with innate defense components present in saliva or serum.…”