Platelet-endothelial interactions in inflamed mesenteric venules

Area of Science:

• Immunology
• Cell Biology
• Hematology

Background:

• Selectins are key membrane glycoproteins mediating cell adhesion in inflammation.
• Previous work showed platelets rolling on P-selectin on stimulated endothelium.
• The roles of platelet and endothelial selectins in platelet-endothelial interactions during inflammation require further elucidation.

Purpose of the Study:

• To investigate the function of platelet and endothelial selectins (P- and E-selectins) in platelet-endothelial interactions during inflammation.
• To determine the role of platelet P-selectin in leukocyte recruitment to inflammatory sites.

Main Methods:

• Intravital microscopy of TNF-alpha-inflamed venules.
• Bone marrow reconstitution experiments in P/E-selectin deficient mice using wild-type or P-selectin deficient bone marrow.
• Analysis of platelet-endothelial and platelet-leukocyte interactions.

Main Results:

• Resting platelets interact with both P- and E-selectins on inflamed endothelium.
• Leukocyte fucosyltransferases FucT IV and FucT VII do not confer selectin ligand activity to platelets.
• Activated platelet P-selectin mediates interactions with an endothelial ligand.
• Platelet P-selectin did not rescue the immunodeficient phenotype in P/E-selectin deficient mice, indicating no active role in leukocyte recruitment.

Conclusions:

• Platelets engage with endothelial P- and E-selectins during inflammation.
• Platelet P-selectin is not essential for leukocyte recruitment to inflammatory sites.
• Platelets may utilize endothelial selectins for participation in inflammatory and hemostatic processes.