Localization of the mouse defense lectin ficolin B in lysosomes of activated macrophages

Abstract

Ficolins are pattern-recognition molecules of the innate immune system able to trigger the lectin pathway of the complement activation upon binding to microbial surfaces. In humans, two plasma ficolins have been identified and characterized, whereas a third cell-associated ficolin (M-ficolin) was found on monocyte surfaces. The mouse homologue of M-ficolin is called ficolin B. Although the spatial-temporal expression patterns of mouse ficolins have been described recently, the subcellular localization of ficolin B protein is so far unknown. By using ficolin B-specific antibodies and confocal microscopy, we show that ficolin B is expressed within mouse peritoneal exudate macrophages and is co-localized with Lamp-1, a marker for lysosomes and late endosomes. In addition, the data indicate that ficolin B expression is up-regulated upon macrophage activation.

Mice Deficient in Ficolin, a Lectin Complement Pathway Recognition Molecule, Are Susceptible to Streptococcus pneumoniae Infection

“…This suggests that FcnB can potentially work more effectively via primitive opsonophagocytosis. This speculation might be supported by the observation that FcnB was colocalized with Lamp-1, a marker for lysosomes and late endosomes in macrophages (37). The orthology between FcnB and M-FCN predicts that M-FCN deficiency would result in the increased susceptibility to pneumococcal infection in humans.…”

“…Several explanations are possible to explain the discrepancy between low survival rate in the Fcnb 2/2 mice and normal complement activation activity in their sera. First, it is known that FcnB expression is upregulated upon macrophage activation (37), and that the expression of M-FCN (human ortholog of FcnB) is induced several times in monocyte-derived macrophages after treatment with TLR2 and TLR4 ligands (38). Second, FcnB might execute its defensive function at the local site of lung rather than in the circulation.…”

The Recognition Unit of FIBCD1 Organizes into a Noncovalently Linked Tetrameric Structure and Uses a Hydrophobic Funnel (S1) for Acetyl Group Recognition

“…A pH-dependent conformational switch in the binding of ligand was observed in M-ficolin, and a two-state conformational equilibrium model depending on the charged state of histidines in the acetyl-binding region was proposed to facilitate ligand release at low pH in acidic compartments (17). The physiological relevance of this was underlined by the recent finding of ficolin-B (the murine counterpart to M-ficolin) in lysosomes of activated macrophages (47). FIBCD1 facilitates the endocytosis of acetylated BSA (1), and the direction of acetylated components for degradation in the endosome would require ligand release, which would consecutively allow FIBCD1 to be recirculated to the membrane.…”

Secreted M-Ficolin Anchors onto Monocyte Transmembrane G Protein-Coupled Receptor 43 and Cross Talks with Plasma C-Reactive Protein to Mediate Immune Signaling and Regulate Host Defense

“…However, their varied locations in assorted tissues and species are suggestive of their differential functions. Notably, the tissue distribution and function of the human M-ficolin and its homologue (ficolin b) in pigs (23) and mice (24) are substantially different (25). Hitherto, no consensus has been reached on the subcellular localization and fate of M-ficolin in human monocytes, whether intracellular in secretory granules (19,20), on the cell surface (18), or secreted into the serum (26), although the localization of M-ficolin in the neutrophils was recently reported (19).…”