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Published on: June 29, 2016
Mannose-binding lectin binds IgM to activate the lectin complement pathway in vitro and in vivo
Meghan E McMullen1, Melanie L Hart, Mary C Walsh
1Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
This study reveals that both mannose-binding lectin (MBL) and immunoglobulin M (IgM) are crucial for initiating complement activation during gastrointestinal ischemia/reperfusion injury. Their combined presence drives lectin pathway activation and subsequent tissue damage.
Area of Science:
- Immunology
- Complement System Biology
- Ischemia/Reperfusion Injury Mechanisms
Background:
- The lectin pathway, initiated by mannose-binding lectin (MBL), is implicated in ischemia/reperfusion (I/R) injury.
- Previous research suggested immunoglobulin M (IgM) and the classical complement pathway initiate I/R-induced complement activation.
- The interplay between MBL and IgM in complement activation following I/R remained unclear.
Purpose of the Study:
- To investigate the interaction between MBL and IgM in initiating complement activation.
- To determine the combined role of MBL and IgM in ischemia/reperfusion injury.
Main Methods:
- Surface plasmon resonance to assess MBL-IgM binding.
- In vitro complement activation assays using sensitized red blood cells and endothelial cells.
- In vivo studies in mice using gastrointestinal I/R models with varying MBL and IgM levels.
Main Results:
- MBL directly binds to human IgM.
- Combined IgM and MBL activate the lectin pathway in vitro, leading to C4 deposition.
- Mice lacking both IgM and MBL showed reduced complement activation and injury in a gastrointestinal I/R model when MBL was reintroduced.
Conclusions:
- MBL and IgM cooperate to activate the lectin pathway.
- Both IgM and MBL are essential for complement activation and injury following gastrointestinal ischemia/reperfusion.
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