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The molecular interaction between M- and L-ficolin and chitin
Anne Trommelholt Jepsen1, Theresa Thomsen1, Anders Schlosser1, Grith Lykke
Sørensen1, Steffen Thiel2, and Uffe Holmskov1.
1
2
Medical Biotechnology Center, University of Southern Denmark, Odense, Denmark.
Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark.
M- and L-ficolin are pattern recognition molecules capable of initiating the lectin
pathway of the complement system. M-ficolin is predominantly associated to leucocytes
and alveolar epithelium whereas L-ficolin is mainly a serum protein. M- and L-ficolin
both recognize acetylated compounds including N-acetylglucosamine (GlcNAc), through
the fibrinogen related domain (FReD) in the C-terminus.
Chitin is a linear homopolymer of β-1,4-linked GlcNAc, which next to cellulose
is the most abundant known biopolymer. Vertebrates are exposed to chitin both through
food ingestion and when infected with parasites, and fungi. Chitin has recently been
identified as a pathogen-associated molecular pattern (PAMP) that modulates the allergic
response in mice, and we hypothesized that chitin would serve as ligand for ficolins.
Our initial observations have demonstrated that recombinant M-ficolin binds
specifically to chitin and that the binding can be abolished by the addition of acetate. The
further investigation of the acetyl-binding of M- and L-ficolin are carried out through
mutations of essential amino acids in the putative binding sites predicted on the basis of
known FReD acetyl interaction. The binding of the mutated variants of M- and L-ficolin
to acetylated bovine serum albumin (BSA) and chitin will be analyzed by ELISA and
pull-down experiments, respectively.
The prospects of our observation is that M-ficolin may play an important role in
the innate defence against inhaled fungi by chitin interaction, and the resulting
modulation the pulmonary immune response.