The innate pattern recognition molecule Ficolin-1 is secreted by monocytes/macrophages and is circulating in human plasma

Honoré, Christian; Rørvig, Sara; Munthe-Fog, Lea; Hummelshøj, Tina; Madsen, Hans O.; Borregaard, Niels; Garred, Peter

doi:10.1016/j.molimm.2008.02.005

Cited by 86 publications

(94 citation statements)

References 20 publications

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“…Moreover, the ficolin-1 concentrations correlated significantly between the two methods (Spearman's r ¼ 0.7532, Po0.0001) (data not shown). When the samples were depleted for ficolin-2 as described in our original report showing ficolin-1 in plasma, 10 which involved prolonged incubation of anti-ficolin-2 antibodies with protein A beads, we observed a median concentration of 0.09 mg ml À 1 using our new in-house assay and 0.07 mg ml À 1 for the commercial assay (data not shown).…”

Section: Plasma Levels Of Ficolin-1mentioning

confidence: 52%

“…We previously reported the median ficolin-1 concentration to be 0.06 mg ml À 1 in a small study comprising eight normal individuals using an assay where ficolin-2 had to be depleted prior to the analysis due to a cross-reactive capture antibody. 10 Using the same procedure, we depleted samples for ficolin-2 prior to ficolin-1 assessment in both the new ficolin-1 assay and the commercial one. We observed that the concentration of ficolin-1 was approximately four-fold decreased compared with native plasma compatible with the concentrations observed in our original article.…”

Section: Discussionmentioning

confidence: 99%

“…[6][7][8] Ficolin-1 has a preference for sialic acid 9 and binds to sialicacid-containing structures present on living monocytes and granulocytes. 10 A highly conserved cysteine residue in the collagen-like domain enables all three ficolins to form complexes with the mannosebinding lectin/ficolin-associated serine proteases named MASPs and hence to activate the complement cascade through the lectin pathway. 1 However, the potential to activate complement differs among the ficolins, ficolin-3 being the most potent, ficolin-2 intermediate and ficolin-1 displaying least complement activation potential.…”

mentioning

confidence: 99%

“…20 Both neutrophils and monocytes secrete ficolin-1 to the surroundings where it may have a role in local immune defence. 10,17,18,21 The FCN1 gene is well conserved between invertebrates, mouse and human, suggesting crucial and fundamental roles of ficolin-1.…”

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confidence: 99%

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Variation in FCN1 affects biosynthesis of ficolin-1 and is associated with outcome of systemic inflammation

et al. 2012

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Ficolin-1 is a recognition molecule of the lectin complement pathway. The ficolin-1 gene FCN1 is polymorphic, but the functional and clinical consequences are unknown.The concentration of ficolin-1 in plasma and FCN1 polymorphisms in positions À 1981 (rs2989727), À 791 (rs28909068), À 542 (rs10120023), À 271 (rs28909976), À 144 (rs10117466) and þ 7918 (rs1071583) were determined in 100 healthy individuals. FCN1 expression by isolated monocytes and granulocytes and ficolin-1 levels in monocyte culture supernatants were assessed in 21 FCN1-genotyped individuals. FCN1 polymorphisms were determined in a cohort of 251 patients with systemic inflammation. High ficolin-1 plasma levels were significantly associated with the minor alleles in position À 542 and À 144. These alleles were also significantly associated with high FCN1 mRNA expression. The level of ficolin-1 in culture supernatants was significantly higher in individuals homozygous for the minor alleles at positions À 542 and À 144. Homozygosity for these alleles was significantly associated with fatal outcome in patients with systemic inflammation. None of the other investigated polymorphisms were associated with FCN1 and ficolin-1 expression, concentration or disease outcome. Functional polymorphic sites in the promoter region of FCN1 regulate both the expression and synthesis of ficolin-1 and are associated with outcome in severe inflammation.

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Section: Plasma Levels Of Ficolin-1mentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Variation in FCN1 affects biosynthesis of ficolin-1 and is associated with outcome of systemic inflammation

et al. 2012

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“…Both FCN1 (M-ficolin) and FCN2 (L-ficolin), located in chromosome 9q34 and separated by 22 kb, were detected in PBMCs, with FCN1 expressed at higher level in PBMCs than FCN2 and also differentially expressed between CFS and control subjects. Although FCN1 has been (until recently) solely associated with monocytes, neutrophils, and spleen cells and hypothesized to be a secretory protein (32), it has recently been found in serum in low concentrations (33). If released by monocytes, FCN1 could bind to a variety of its ligands, acetylated sugars, or proteins, which are abundant during or following exercise (34,35).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Control of Complement Activation in an Exercise Model of Chronic Fatigue Syndrome

Sorensen

Jones

Vernon

et al. 2009

Mol Med

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Complement activation resulting in significant increases of C4a split product may be a marker of postexertional malaise in individuals with chronic fatigue syndrome (CFS). This study focused on identification of the transcriptional control that may contribute to the increased C4a in CFS subjects after exercise. We used quantitative reverse-transcription polymerase chain reaction to evaluate differential expression of genes in the classical and lectin pathways in peripheral blood mononuclear cells (PBMCs). Calibrated expression values were normalized to the internal reference gene peptidylpropyl isomerase B (PPIB), the external reference gene ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL), or the geometric mean (GM) of the genes ribosomal protein, large, P0 (RPLP0) and phosphoglycerate kinase 1 (PGK1). All nine genes tested, except mannose-binding lectin 2 (MBL2), were expressed in PBMCs. At 1 hour postexercise, C4, mannan-binding lectin serine protease 2 (MASP2) and ficolin 1 (FCN1) transcripts were detected at higher levels (≥2-fold) in at least 50% (4 of 8) of CFS subjects and were detected in 88% (7 of 8) CFS subjects when subjects with overexpression of either C4 or MASP2 were combined. Only an increase in the MASP2 transcript was statistically significant (PPIB, P = 0.001; GM, P = 0.047; rbcL, P = 0.045). This result may be due to the significant but transient downregulation of MASP2 in control subjects (PPIB, P = 0.023; rbcL, P = 0.027). By 6 hours postexercise, MASP2 expression was similar in both groups. In conclusion, lectin pathway responded to exercise differentially in CFS than in control subjects. MASP2 downregulation may act as an antiinflammatory acute-phase response in healthy subjects, whereas its elevated level may account for increased C4a and inflammation-mediated postexertional malaise in CFS subjects.

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Purification, Measurement of Concentration, and Functional Complement Assay of Human Ficolins

Matsushita

Kilpatrick

Shiraki

et al. 2013

The Complement System

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Ficolins constitute a group of lectins involved in innate immunity. L-Ficolin, H-ficolin, and M-ficolin are present in human serum. The human ficolins differ in carbohydrate-binding specificity, but they have in common the ability to recognize the acetyl group. L-Ficolin and H-ficolin are associated with serine proteases termed MASPs (MBL-associated serine proteases) and their truncated proteins, and the complexes (L/H-ficolin-MASP) activate the lectin pathway of complement upon binding to their ligands. Recombinant M-ficolin is also able to form a complex with MASP, resulting in complement activation. L-Ficolin and H-ficolin can be purified as a complex with MASP from serum by utilizing their binding specificities. These ficolin-MASP complexes have an ability to activate C4. Human ficolins are quantified by ELISA using specific antibodies or ligands.

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The innate pattern recognition molecule Ficolin-1 is secreted by monocytes/macrophages and is circulating in human plasma

Cited by 86 publications

References 20 publications

Variation in FCN1 affects biosynthesis of ficolin-1 and is associated with outcome of systemic inflammation

Variation in FCN1 affects biosynthesis of ficolin-1 and is associated with outcome of systemic inflammation

Transcriptional Control of Complement Activation in an Exercise Model of Chronic Fatigue Syndrome

Purification, Measurement of Concentration, and Functional Complement Assay of Human Ficolins

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