An assay for the mannan-binding lectin pathway of complement activation

Petersen, Steen V.; Thiel, Steffen; Jensen, Lisbeth; Steffensen, Rudi; Jensenius, Jens C.

doi:10.1016/s0022-1759(01)00453-7

Cited by 195 publications

(153 citation statements)

References 27 publications

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“…6C). Furthermore, compared with the correlation coefficient of MBL levels and MASP-2 activation in 100 control samples (30,38), the C4 activation by MASP-2 was already suboptimal in the neutropenic patients before (visit 1) MBL infusion (r 2 ϭ 0.728, p ϭ 0.08), even though MASP-2 binding to MBL was not impaired in these samples. Median MASP-2 activation per microgram of MBL in the patients before and 15 min after MBL infusion and in the controls can be found in Table II.…”

Section: Masp-2 Activity In Oncology Patientsmentioning

confidence: 94%

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Mannose-Binding Lectin (MBL) Substitution: Recovery of Opsonic Function In Vivo Lags behind MBL Serum Levels

Brouwer

Frakking

Wetering

et al. 2009

The Journal of Immunology

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Mannose-binding lectin (MBL) deficiency is often associated with an increased risk of infection or worse prognosis in immunocompromised patients. MBL substitution in these patients might diminish these risks. We therefore performed an open, uncontrolled safety and pharmacokinetic MBL-substitution study in 12 pediatric oncology patients with chemotherapy-induced neutropenia. Twice weekly MBL infusions with plasma-derived MBL yielded MBL trough levels >1.0 μg/ml. We tested whether MBL substitution in vivo increased MBL-dependent complement activation and opsonophagocytosis of zymosan in vitro. Upon MBL substitution, opsonophagocytosis by control neutrophils increased significantly (p < 0.001) but remained suboptimal, although repeated MBL infusions resulted in improvement over time. The MBL-dependent MBL-associated serine protease (MASP)-mediated complement C3 and C4 activation also showed a suboptimal increase. To explain these results, complement activation was studied in detail. We found that in the presence of normal MASP-2 blood levels, MASP-2 activity (p < 0.0001) was reduced as well as the alternative pathway of complement activation (p < 0.05). This MBL-substitution study demonstrates that plasma-derived MBL infusions increase MBL/MASP-mediated C3 and C4 activation and opsonophagocytosis, but that higher circulating levels of plasma-derived MBL are required to achieve MBL-mediated complement activation comparable to healthy controls. Other patient cohorts should be considered to demonstrate clinical efficacy in phase II/III MBL-substitution studies, because we found a suboptimal recovery of (in vitro) biological activity upon MBL substitution in our neutropenic pediatric oncology cohort.

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Section: Masp-2 Activity In Oncology Patientsmentioning

confidence: 94%

“…In this assay, as described by Petersen et al (30), the specific C4b-depositing capacity of the MBL pathway was determined by incubating serum samples FIGURE 1. MBL substitution regimen.…”

Section: Complement Activation Assaysmentioning

confidence: 99%

Mannose-Binding Lectin (MBL) Substitution: Recovery of Opsonic Function In Vivo Lags behind MBL Serum Levels

Brouwer

Frakking

Wetering

et al. 2009

The Journal of Immunology

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“…Lectin pathway activation was quantified using the C4 deposition assay developed by Petersen et al (34). MBL and ficolin-depleted serum was generated by incubating fresh human serum with D-Mannose-agarose beads (Sigma) and N-Acetyl-D-glucosamine-agarose beads (Sigma).…”

Section: Complement C4 Activation and Deposition Assaymentioning

confidence: 99%

Specifically Binding of L-ficolin to N-glycans of HCV Envelope Glycoproteins E1 and E2 Leads to Complement Activation

Liu

Ali

et al. 2009

Cell Mol Immunol

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L-ficolin, one of lectin families, is a recently identified complement factor that initiates lectin pathway of complement. Little is known about its role in viral hepatitis. In the present study, we found that L-ficolin in serum from 103 patients with hepatitis C virus (HCV), were significantly higher than that in 150 healthy controls. We further found that L-ficolin expressions were significantly increased in vitro study by HCV JFH-1 infected human hepatocyte cell line Huh7.5.

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“…5C). Additionally, the C4b deposition ability of PO25RP after binding to PO25 LPS or mannan, in conditions excluding participation of C1, [18] was demonstrated (Fig. 5D).…”

Section: Activation Of the Complement-lectin Pathwaymentioning

confidence: 92%

“…C4b deposition property via LP was determined in ELISA according to the method described by Petersen et al, in conditions excluding participation of C1 [18]. Briefly, PO25RP or mouse serum diluted in MBL-binding buffer was incubated in mannan-or PO25 LPS-coated ELISA plates, which was followed by incubation with 5 ?…”

Section: +mentioning

confidence: 99%

Role of the complement‐lectin pathway in anaphylactoid reaction induced with lipopolysaccharide in mice

et al. 2003

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We show that Proteus vulgaris O25 (PO25) lipopolysaccharide (LPS) induced an anaphylactoid reaction not only in wild-type and in lipid A non-responding mice but also in recombinase-activating gene-2-deficient (RAG-2 -/-) and in mast cell-deficient (W/Wv) animals. Western blot analysis indicated that PO25 LPS bound to Ra-reactive factor (RaRF), the complex of mannan-binding lectins (MBL) and MBL-associated serine proteases. Binding of RaRF to PO25 LPS led to the activation of C4 component without participation of either C1 or Ig, via the lectin pathway. Relative concentration of RaRF and hemolytic activity in mouse serum decreased rapidly during the process of anaphylactoid reaction. A significant drop of MBL-A, but not MBL-C level was observed. Administration with antiserum to RaRF prevented animals from death as a consequence of the inhibition of interaction of RaRF with the carbohydrate target and complement activation. These results indicate that complementlectin pathway activation is responsible for the anaphylactoid reaction induced with LPS in muramyldipeptide-primed mice. RaRF also activated fibrinogen in vitro suggesting the involvement of the coagulation system in the process investigated.

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An assay for the mannan-binding lectin pathway of complement activation

Cited by 195 publications

References 27 publications

Mannose-Binding Lectin (MBL) Substitution: Recovery of Opsonic Function In Vivo Lags behind MBL Serum Levels

Mannose-Binding Lectin (MBL) Substitution: Recovery of Opsonic Function In Vivo Lags behind MBL Serum Levels

Specifically Binding of L-ficolin to N-glycans of HCV Envelope Glycoproteins E1 and E2 Leads to Complement Activation

Role of the complement‐lectin pathway in anaphylactoid reaction induced with lipopolysaccharide in mice

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