Fucosylated clusterin in semen promotes the uptake of stress-damaged proteins by dendritic cells via DC-SIGN

MERLOTTI IPPÓLITO, ANTONELLA; DANTAS, EZEQUIEL; REMES LENICOV, FEDERICO; CEBALLOS, ANA; JANCIC, CAROLINA; VARESE, AUGUSTO; RUBIONE, JULIA; STOVER, SOFIA; GEFFNER, JORGE; SABATTE, JUAN

HUMAN REPRODUCTION

OXFORD UNIV PRESS

Lugar: Oxford; Año: 2015 vol. 30 p. 1545 - 1556

0268-1161

Study question: Could seminal plasma clusterin play a role in the uptake of stress-damaged proteins by dendritic cells? Summary answer: Seminal plasma clusterin, but not serum clusterin, promotes the uptake of stress-damaged proteins by dendritic cells via DC-SIGN. What is known already: Clusterin is one of the major extracellular chaperones. It interacts with a variety of stressed proteins to prevent their aggregation, guiding them for receptor-mediated endocytosis and intracellular degradation. The concentration of clusterin in semen is almost 20-fold higher than that found in serum, raising the question about the role of seminal plasma clusterin in reproduction. No previous studies have analyzed whether seminal plasma clusterin has chaperone activity. We have previously shown that seminal plasma clusterin, but not serum clusterin, expresses an extreme abundance of fucosylated glycans. These motifs enable seminal plasma clusterin to bind DC-SIGN with very high affinity. Study design, size, duration: In vitro experiments were performed to evaluate the ability of seminal plasma clusterin to inhibit the precipitation of stressed proteins, promoting their uptake by dendritic cells via DC-SIGN (a C-type lectin receptor selectively expressed on dendritic cells (DC)). Moreover, the ability of seminal plasma clusterin to modulate the phenotype and function of DCs was also assessed. Participants/materials, setting, methods: Clusterin was purified from human semen and human serum. Catalase, bovine serum albumin, glutathione S-transferase, and normal human serum were stressed and the ability of seminal plasma clusterin to prevent the precipitation of these proteins, guiding them to DC-SIGN expressed by DCs, was evaluated by fluorescence-activated cell sorter (FACS). Endocytosis of stressed proteins was analyzed by confocal microscopy and the ability of seminal plasma clusterin-treated DCs to stimulate the proliferation of CD25+FOXP3+CD4+ T cells was also evaluated by FACS. Main results and the role of chance: Seminal plasma clusterin interacts with stressed proteins, inhibits their aggregation (p