CD44 is a physiological E-selectin ligand on neutrophils

Area of Science:

• Immunology
• Cell Biology
• Glycobiology

Background:

• Selectins are crucial for immune cell trafficking to inflammation sites.
• The E-selectin ligands on polymorphonuclear neutrophils (PMNs) are not fully understood.
• CD44 is an adhesion molecule with potential roles in leukocyte extravasation.

Purpose of the Study:

• To characterize E-selectin ligands on PMNs.
• To investigate the role of CD44 in PMN extravasation and selectin-mediated adhesion.
• To explore CD44 as a potential therapeutic target in selectin-related diseases.

Main Methods:

• Immunopurification of CD44 from differentiated cells and peripheral blood PMNs.
• E-selectin binding assays.
• Analysis of glycans mediating CD44 binding.
• In vivo studies of leukocyte rolling and recruitment in mouse models of inflammation.
• Analysis of CD44 in a patient with leukocyte adhesion deficiency type II.

Main Results:

• CD44 purified from PMNs binds specifically to E-selectin.
• This binding is mediated by specific N-linked glycans (sialylated, alpha(1,3) fucosylated).
• CD44 facilitates leukocyte rolling on E-selectin in vivo and cooperates with PSGL-1 in neutrophil recruitment.
• CD44 is hypofucosylated in PMNs from a patient with leukocyte adhesion deficiency type II.

Conclusions:

• CD44 functions as an E-selectin ligand on PMNs, contributing to leukocyte recruitment.
• Cell-specific posttranslational modifications of CD44 influence its E-selectin binding.
• CD44 plays a significant role in the innate immune response.
• CD44 represents a potential therapeutic target for selectin-dependent inflammatory diseases.