INHIBITION OF INTEGRIN VLA-3 AND TETRASPANIN CD151 PROTECTS AGAINST NEUTROPHIL-MEDIATED ENDOTHELIAL DAMAGE

Area of Science:

• Immunology
• Cell Biology
• Vascular Biology

Background:

• Neutrophil recruitment to injury sites is essential but can cause vascular damage in sepsis.
• Activated neutrophils interacting with endothelial cells can lead to significant vascular injury.
• Identifying molecules involved in neutrophil diapedesis offers therapeutic targets for critical illness.

Purpose of the Study:

• To test if inhibiting neutrophil very late antigen-3 (VLA-3; α3β1) and CD151 protects endothelial function from neutrophil-mediated damage.
• To investigate the role of VLA-3 and CD151 in neutrophil-induced endothelial dysfunction.

Main Methods:

• Blood from septic patients and healthy donors was used to isolate neutrophils.
• Human umbilical vascular endothelial cells were activated with TNF-α and their resistance measured using electric cell impedance sensing.
• Neutrophils were treated with blocking antibodies against VLA-3 and/or CD151 before co-culture with endothelial cells.

Main Results:

• Neutrophils from septic patients or activated ex vivo caused greater endothelial monolayer damage than healthy neutrophils.
• Antibody blockade of VLA-3 and/or CD151 significantly reduced neutrophil-induced endothelial damage.
• These protective effects were observed across various substrates (fibronectin, collagen, laminin), indicating broad tissue relevance.

Conclusions:

• Very late antigen-3 (VLA-3) and CD151 on activated human neutrophils are key mediators of endothelial damage.
• Targeting VLA-3 and CD151 may represent a therapeutic strategy to preserve endothelial and organ function in critical illness.