Mannose-binding lectin has a direct deleterious effect on ischemic brain microvascular endothelial cells

Area of Science:

• Neuroscience
• Immunology
• Cell Biology

Background:

• Mannose-binding lectin (MBL) initiates the lectin pathway and is implicated in ischemic stroke.
• MBL deposition on ischemic endothelium suggests its involvement, but downstream effects remain unclear.

Purpose of the Study:

• To investigate the direct interactions between MBL and ischemic brain endothelial cells.
• To elucidate the mechanisms by which MBL affects endothelial cells under ischemic conditions.

Main Methods:

• Human brain microvascular endothelial cells (hBMECs) were subjected to hypoxia or oxygen-glucose deprivation (OGD).
• Cells were re-oxygenated with human serum or recombinant MBL (rhMBL).
• MBL deposition, complement activation (C3c), cell viability, and cytoskeletal organization were assessed using microscopy and cell assays.

Main Results:

• Hypoxic/OGD hBMECs showed increased MBL deposition and complement activation compared to normoxic controls.
• Re-oxygenation with rhMBL significantly reduced cell viability in both hypoxia (-25%) and OGD (-34%) conditions, indicating a direct toxic effect.
• MBL internalization and altered cytoskeletal organization were observed in hypoxic cells, suggesting direct structural impact.

Conclusions:

• MBL exerts a direct, deleterious effect on ischemic brain endothelial cells in vitro.
• This toxic effect of MBL occurs independently of complement activation.
• MBL's direct interaction with endothelial cells contributes to its detrimental role in ischemic stroke pathophysiology.