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Mannan-binding lectin (MBL)-mediated opsonization is enhanced by the alternative pathway amplification loop.
Nannette Brouwer1, Koert M Dolman, Rob van Zwieten
1Sanquin Research-Academic Medical Centre Landsteiner Laboratory, Amsterdam, The Netherlands. n.brouwer@sanquin.nl
Molecular Immunology
|February 28, 2006
Summary
Mannose-binding lectin (MBL) deficiency impacts the innate immune system. This study found MBL-mediated complement activation requires the alternative pathway amplification loop for effective zymosan opsonization.
Area of Science:
- Immunology
- Innate Immunity
- Complement System
Background:
- The complement system, crucial for innate immunity, has three activation pathways: classical, lectin, and alternative.
- Mannose-binding lectin (MBL) deficiency can impair lectin pathway activation.
- MBL plays a role in recognizing pathogens like yeast.
Purpose of the Study:
- To investigate MBL deficiency in a Caucasian cohort.
- To explore the role of the alternative pathway amplification loop in MBL-mediated opsonization of zymosan.
- To determine the MBL plasma concentration threshold for deficiency.
Main Methods:
- MBL genotyping and plasma concentration measurements in healthy donors.
- Western blot analysis for MBL recognition of zymosan.
- Flow cytometry-based opsonophagocytosis assay using MBL-, factor D-, and properdin-deficient sera.
Main Results:
- An optimal MBL deficiency cut-off was determined at 0.7 microg/ml, with 38% of the cohort below this level.
- MBL-sufficient sera showed high MBL oligomers on zymosan, unlike MBL-deficient sera.
- Opsonophagocytosis was reduced in MBL-, factor D-, and properdin-deficient sera but restored upon adding purified components.
Conclusions:
- MBL-mediated complement activation is dependent on the alternative pathway amplification loop for optimal zymosan opsonization.
- This pathway functions even at low serum concentrations.
- MBL deficiency is prevalent in the studied Caucasian population.