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07:09
Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
Published on: January 7, 2019
The down-stream effects of mannan-induced lectin complement pathway activation depend quantitatively on alternative
Morten Harboe1, Peter Garred, Ellen Karlstrøm
1Institute of Immunology, University of Oslo and Rikshospitalet University Hospital, NO-0027 Oslo, Norway.
Molecular Immunology
|October 6, 2009
Summary
The lectin pathway
Area of Science:
- Immunology
- Complement System Biology
Background:
- Complement activation is crucial in human disease.
- The alternative pathway (AP) amplifies classical pathway (CP) effects.
- The AP's role in mannan-induced lectin pathway (LP) activation is unclear.
Purpose of the Study:
- To investigate the role of AP amplification in LP activation.
- To delineate the mechanisms of mannan-induced LP activation.
- To assess AP's contribution to downstream complement effects.
Main Methods:
- Utilized mannan on solid phase to activate LP in normal human serum.
- Employed monoclonal antibodies for inhibition experiments.
- Measured terminal complement complex (TCC) generation in fluid and solid phases.
Main Results:
- LP activation was MBL-dependent, as anti-MBL mAb 3F8 abolished TCC generation.
- Blocking AP with anti-factor D inhibited >80% of fluid-phase TCC after LP activation.
- AP amplification was essential for TCC generation in LP, even during C2 bypass.
Conclusions:
- The lectin pathway's downstream effects heavily rely on alternative pathway amplification in normal serum.
- AP amplification is critical for LP function, including in C2 bypass scenarios.
- Understanding this interplay is key for pathophysiology and therapeutic strategies.
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