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Mannose-binding lectin null alleles are associated with preserved epithelial cell integrity following intestinal

R A Matthijsen1, J P M Derikx, R Steffensen

  • 1Department of Surgery, Maastricht University Medical Centre & School for Nutrition & Metabolism (NUTRIM), Maastricht, The Netherlands.

Molecular Immunology
|May 30, 2009
PubMed

Insights

Mannose-binding lectin (MBL) deficiency significantly reduces intestinal cell damage following ischemia-reperfusion (IR) injury in humans. This suggests MBL impacts intestinal epithelial integrity directly, independent of complement activation.

Area of Science:

  • Immunology
  • Gastroenterology
  • Cell Biology

Background:

  • Mannose-binding lectin (MBL) deficiency is linked to reduced intestinal ischemia-reperfusion (IR) damage in animal models.
  • Understanding MBL's role in human intestinal IR injury is crucial for clinical management.

Purpose of the Study:

  • To investigate the association between MBL deficiency and intestinal cell damage in humans undergoing IR.
  • To explore the immediate, non-complement dependent effects of MBL on intestinal epithelial integrity during IR.

Main Methods:

  • A novel human small intestine IR model was used with 29 patients.
  • MBL genotype (quantitative-PCR), enterocyte loss (plasma I-FABP), and MBL levels/deposition were assessed.
  • Epithelial cell damage was correlated with MBL genotype.

Main Results:

  • Significant variation in epithelial cell damage was observed across different MBL genotypes (p=0.02).
  • Homozygous wildtype individuals showed twice the I-FABP release compared to heterozygous and ten times that of homozygous variant individuals (p=0.03, p=0.04).
  • No MBL deposition was detected during reperfusion, indicating a non-complement dependent mechanism.

Conclusions:

  • MBL influences intestinal epithelial cell integrity during IR in an immediate, non-complement dependent manner.
  • MBL deficiency is associated with significantly reduced intestinal cell damage in humans.
  • These findings highlight MBL as a potential therapeutic target for intestinal IR injury.

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