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Peptides which bind to E-selectin and block neutrophil adhesion
C L Martens1, S E Cwirla, R Y Lee
1Affymax Research Institute, Palo Alto, California 94304, USA.
The Journal of Biological Chemistry
|September 8, 1995
Summary
Researchers identified novel peptide ligands that bind to E-selectin, inhibiting neutrophil adhesion. These peptides show therapeutic potential for controlling inflammatory responses by reducing neutrophil migration.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- E-selectin is an inducible cell adhesion molecule crucial for neutrophil rolling on the endothelium during inflammation.
- Inhibiting selectin-mediated rolling offers a therapeutic strategy for inflammation-induced diseases.
Purpose of the Study:
- To identify and optimize novel E-selectin ligands using recombinant peptide library screening.
- To evaluate the therapeutic potential of identified peptide ligands in preclinical models of inflammation.
Main Methods:
- Recombinant peptide library screening was employed to discover E-selectin ligands.
- Binding affinity (Kd) was determined, and inhibitory effects on neutrophil adhesion were assessed in static and flow-cell assays.
- In vivo efficacy was tested in a mouse model of acute inflammation.
Main Results:
- Novel peptides with high binding affinity (low nanomolar Kd) for E-selectin were identified.
- These peptides effectively blocked E-selectin-mediated neutrophil adhesion in vitro.
- Administration of a lead peptide significantly reduced neutrophil transmigration in an acute inflammatory mouse model.
Conclusions:
- Peptide ligands targeting E-selectin can be effectively identified and optimized using library screening.
- These novel peptides demonstrate therapeutic potential for managing inflammatory conditions by inhibiting neutrophil recruitment.
- The findings suggest that E-selectin's natural ligand may involve both protein and carbohydrate components.